RESUMO
Neurogenesis in the dentate gyrus is sensitive to endogenous and exogenous factors that influence hippocampal function. Ongoing neurogenesis and the integration of these new neurons throughout life thus may provide a sensitive indicator of environmental stress. We examined the effects of Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls (PCBs), on the development and function of newly generated dentate granule cells. Early exposure to A1254 has been associated with learning impairment in children, suggesting potential impact on the development of hippocampus and/or cortical circuits. Oral A1254 (from the 6th day of gestation to postnatal day 21) produced the expected increase in PCB levels in brain at postnatal day 21, which persisted at lower levels into adulthood. A1254 did not affect the proliferation or survival of newborn neurons in immature animals nor did it cause overt changes in neuronal morphology. However, A1254 occluded the normal developmental increase in sEPSC frequency in the third post-mitotic week without altering the average sEPSC amplitude. Our results suggest that early exposure to PCBs can disrupt excitatory synaptic function during a period of active synaptogenesis, and thus could contribute to the cognitive effects noted in children exposed to PCBs.
Assuntos
/toxicidade , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Neurônios/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Sinapses/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Neurônios/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Sinapses/fisiologia , Hormônios Tireóideos/metabolismoRESUMO
The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling.
Assuntos
Cognição/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Memória/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Éteres Difenil Halogenados/toxicidade , Humanos , Fenóis/toxicidade , Bifenilos Policlorados/toxicidade , Comportamento SocialRESUMO
OBJECTIVES: To determine prevalence of short-term postpartum anal incontinence after obstetrical anal sphincter injury and prognostic factors. MATERIALS AND METHODS: Retrospective study including every patient with an obstetrical anal sphincter injury between January 2006 and December 2012 in one tertiary maternity unit. Patients were interviewed and examined at 2-month postpartum. Anal incontinence was defined by the presence of at least one of the following symptoms: flatus incontinence, faecal incontinence and faecal urgency. RESULTS: Among 17,110 patients who delivered vaginally during period study, 134 (0.8%) presented an anal sphincter injury. Postpartum obstetrical data were available for 110 of them. Among those patients, 50 women (45.5%) had at least one symptom of anal incontinence at 2-month postpartum and 8 (7.3%) had faecal incontinence. Only maternal age and second stage duration were significantly associated with anal incontinence after obstetrical anal sphincter injury. The degree of sphincter damage at delivery (IIIa, b, c, IV) was not associated with the risk of anal incontinence at 2-month postpartum. CONCLUSION: Maternal age and second stage duration were the only risk factor for anal incontinence after obstetrical anal sphincter injury in this study. High prevalence of anal incontinence at 2-month postpartum of obstetrical anal sphincter injury is observed no matter what is the degree of anal sphincter damage. Our results highlight the importance to diagnose all obstetrical anal sphincter injuries whatever the degree of damage.
Assuntos
Canal Anal/lesões , Incontinência Fecal/epidemiologia , Segunda Fase do Trabalho de Parto , Idade Materna , Complicações do Trabalho de Parto/epidemiologia , Períneo/lesões , Transtornos Puerperais/epidemiologia , Adulto , Incontinência Fecal/etiologia , Feminino , França/epidemiologia , Humanos , Gravidez , Prognóstico , Transtornos Puerperais/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: Neuropeptide FF (NPFF) and its receptors (NPFF1 R and NPFF2 R) are differentially distributed throughout the central nervous system. NPFF reduces cortical excitability in rats when administered intracerebroventricularly (i.c.v.), and both NPFF and NPFF1 R antagonists attenuate pilocarpine-induced limbic seizures. In this study, our aim was to determine whether NPFF exerts anticonvulsant or anti-epileptogenic effects in the rat amygdala kindling model for temporal lobe seizures. METHODS: Male Wistar rats were implanted with a recording/stimulation electrode in the right amygdala and a cannula in the left lateral ventricle. In a first group of animals, the afterdischarge threshold (ADT) was determined after a single i.c.v. infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; n = 10). Subsequently, daily infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; i.c.v.; n = 9) was performed, followed by a kindling stimulus (ADT+200 µA). Afterdischarge duration and seizure severity were evaluated after every kindling stimulus. A second group of rats (n = 7) were fully kindled, and the effect of saline or a high dose of NPFF (10 nmol/h for 2 h, i.c.v.) on ADT and the generalized seizure threshold (GST) was subsequently determined. RESULTS: In naive rats, NPFF significantly increased the ADT compared to control (435 ± 72 µA vs 131 ± 23 µA [P < 0.05]). When rats underwent daily stimulations above the ADT, NPFF did not delay or prevent kindling acquisition. Furthermore, a high dose of NPFF did not alter ADT or GST in fully kindled rats. CONCLUSIONS: I.c.v. administration of NPFF reduced excitability in the amygdala in naive, but not in fully kindled rats, and had no effect on kindling acquisition.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Anticonvulsivantes/farmacologia , Epilepsia do Lobo Temporal/tratamento farmacológico , Excitação Neurológica/efeitos dos fármacos , Oligopeptídeos/farmacologia , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/administração & dosagem , Modelos Animais de Doenças , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Ratos WistarRESUMO
Epidemiological and experimental data highlight the fetal and early postnatal life as critical periods for the effects of endocrine disrupting chemicals (EDCs), since exposure to EDCs during these periods can predispose to disease later in life. EDCs' effects include disorders of the reproductive system throughout life (abnormalities of sexual differentiation, infertility or subfertility and some neoplasia) and disorders of energy balance (obesity and metabolic syndrome). They could also influence the development of the cerebral cortex. However, the demonstration of the involvement of a single EDC remains difficult in human since we are virtually exposed to a mixture of several ubiquitous EDCs which are variably persistent in the environment and the body and have lifelong consequences. Moreover, since their dose-response relationship can be non-monotonic, setting a threshold dose for EDCs effects has become meaningless. Pregnant women, newborns and young children appear to be mostly at risk. However, the role of the physician remains difficult and raises several questions: how can we formulate justified, applicable and updated recommendations that are not counterproductive or alarmist...in a society that has to take the necessary steps to regulate production and protect the population?
Assuntos
Pesquisa Biomédica , Disruptores Endócrinos , Saúde Pública , HumanosRESUMO
The timing of puberty has been mainly studied in females for several reasons, including the possible evaluation of a precise timer (i.e. menarcheal age) and concerns with respect to the high prevalence of precocity in females as opposed to males. Human evidence of altered female pubertal timing after exposure to endocrine disrupting chemicals (EDCs) is equivocal. Among the limiting factors, most studies evaluate exposure to single EDCs at the time of puberty and hardly assess the impact of lifelong exposure to mixtures of EDCs. Some rodent and ovine studies indicate a possible role of foetal and neonatal exposure to EDCs, in accordance with the concept of an early origin of health and disease. Such effects possibly involve neuroendocrine mechanisms because the hypothalamus is a site where homeostasis of reproduction, as well as control of energy balance, is programmed and regulated. In our previous studies, pulsatile gonadotrophin-releasing hormone (GnRH) secretion control via oestrogen, glutamate and aryl hydrocarbon receptors was shown to be involved in the mechanism of sexual precocity after early postnatal exposure to the insecticide dichlorodiphenyltrichloroethane. Very recently, we have shown that neonatal exposure to the potent synthetic oestrogen diethylstilbestrol (DES) is followed by early or delayed puberty depending on the dose, with consistent changes in developmental increase of GnRH pulse frequency. Moreover, DES results in reduced leptin stimulation of GnRH secretion in vitro, an effect that is additive with prenatal food restriction. Thus, using puberty as an endpoint of the effects of EDC, it appears necessary to consider pre- and perinatal exposure to low doses and to pay attention to the other conditions of prenatal life, such as energy availability, keeping in mind the possibility that puberty could not only be advanced, but also delayed through neuroendocrine mechanisms.
Assuntos
Disruptores Endócrinos/efeitos adversos , Hormônio Liberador de Gonadotropina/metabolismo , Hipocampo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Desenvolvimento Sexual/efeitos dos fármacos , Animais , Feminino , HumanosRESUMO
Eating disorders (EDs) are conditions which are becoming more and more widespread among adolescents and they often lead them to seek the opinion of a professional health caregiver, including gynecologists and pediatricians. EDs, and particularly anorexia nervosa (AN), are usually classified as psychological or psychiatric disorders, but they may have major somatic implications and complications as osteoporosis, nutritional deficiencies, cerebral atrophy, cardiac and metabolic disorders. A key issue in the management is prevention or reduction of both the serious somatic consequences and the important mental health consequences (e.g. depression, psychosocial withdrawal, phobia and suicide), integrating different perspectives (psychological or psychiatric - individual and familial -, genetic, nutritional, pediatric, gynecological). Adolescence is a critical period for the onset of EDs though they may also involve younger children. In this case, the consequences on the development (height, weight, puberty) can also be significant. In this review, we will focus on eating disorders in adolescent girls with an emphasis on AN. We describe variations in ED characteristics and their management depending on age at occurrence. A possible ED should be considered by pediatricians consulted about delayed female growth and puberty as well as gynecologists in patients with primary or secondary amenorrhea or infertility.
Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente/fisiologia , Idade de Início , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Gráficos de Crescimento , Humanos , Modelos Biológicos , Pediatria/métodosRESUMO
BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence.
Assuntos
Adamantano/análogos & derivados , Analgésicos Opioides/farmacologia , Dipeptídeos/farmacologia , Tolerância a Medicamentos/fisiologia , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Receptores de Neuropeptídeos/antagonistas & inibidores , Adamantano/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Condicionamento Clássico , Fentanila/farmacologia , Temperatura Alta , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor/tratamento farmacológico , Dor/fisiopatologia , Receptores de Neuropeptídeos/fisiologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/fisiopatologiaRESUMO
The gynaecological issues encountered in children and teenagers lay at the intersection of paediatric endocrinology and gynaecology. More than ten years ago, an outpatient clinic in paediatric endocrinology and gynaecology has been created. Here, we review the last 6 years. 214 girls were included, considering only the first visit for each patient. Collected data are initial concern for this consultation, age at first consultation and confirmed or suspected diagnosis. A classification is done according to the initial concern of patients in six categories. Principal queries concern pubertal development, precocious pilosity or abnormalities in menstrual cycles. Vulvovaginitis and morphologic abnormalities are also frequently encountered. This consultation suggests a paediatric approach with a child feeling confident and a gynaecological examination with a specialist knowing the anatomy particularities and the development of the children. This article focuses on the importance of specific gynaecological examination in children and reviews the main diseases encountered.
Assuntos
Endocrinologia , Exame Ginecológico , Ginecologia , Pediatria , Encaminhamento e Consulta , Adolescente , Serviços de Saúde do Adolescente/organização & administração , Instituições de Assistência Ambulatorial/organização & administração , Bélgica/epidemiologia , Criança , Serviços de Saúde da Criança/organização & administração , Pré-Escolar , Doenças do Sistema Endócrino/diagnóstico , Feminino , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/epidemiologia , Exame Ginecológico/métodos , Exame Ginecológico/normas , Exame Ginecológico/estatística & dados numéricos , Humanos , Lactente , Distúrbios Menstruais/diagnóstico , Distúrbios Menstruais/epidemiologia , Exame Físico/estatística & dados numéricos , Estudos Retrospectivos , Doenças Vaginais/diagnóstico , Doenças Vaginais/epidemiologia , Doenças da Vulva/diagnóstico , Doenças da Vulva/epidemiologia , Adulto JovemRESUMO
Congenital Isolated hypogonadotropic hypogonadism (CIHH) is caused by an inherited mechanism of impairment of the pituitary-gonadal axis, interfering with gonads' control. Currently, different forms of HHCI with (Kallmann syndrome or KS) or without anosmia-hyposmia are known. There are six forms of KS already described but in several cases no genetic mutation is found. The genetic anomalies already described are: KAL1 (locus Xp23) coding for anosmine-1, KAL-2 or FGFRI (8p11. locus 2 - p11.1) coding for Fibroblast Growth Factor Receptor 1 (FGFR1), KAL4 or PROk2 (locus 3p21.1) and KAL3 or ProKR2 (locus 20p13) coding respectively for the Prokinecitin-2 and its receptor, KAL5 or CHD7 (locus_8q12.1) coding for a chromodomain helicase DNA-binding protein-7 gene (CHD7) and lastly KAL6 or FGF8 (10Q 24 loci) coding for Fibroblast Growth Factor 8. The other genetic anomalies without anosmia are less frequent. These are associated either with Gnrhl gene (8p2-11. 2), GnRHR (4q21.2), GPR54 (19p13),TAC3R or neurokinine receptor 3 (4 q 25), LH (19q13.32) or FSH (11p13). The isolated congenital hypogonadotrophic hypogonadism phenotype is variable depending on gender, the importance of the deficit, and ultimately, according to a specific regulatory mechanism of the axis, affected by an inherited genetic anomaly. In this review, we describe the essential aspects of the different phenotypes and genotypes of HHCI, in order to assess clinicians an early disease's diagnosis and management.
Assuntos
Hipogonadismo/congênito , Hipogonadismo/genética , Diagnóstico Diferencial , Aconselhamento Genético , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/terapiaRESUMO
Therapeutic education (TPE) aims to enable the patient suffering from a chronic diseases to manage his/ her illness and treatment, and prevent avoidable complications, while keeping or improving his/her quality of life. It comprises a set de practical tools aiming the patient to acquire skills to manage himself/herself the disease, its care and supervision, in partnership with healthcare providers. TPE may contribute to improve therapeutic compliance and to reduce clinical inertia, two drawbacks frequently encountered in the management of patients with chronic diseases. As an illustration, we briefly present EDUDORA ("Education thérapeutique et préventive face au diabète et a l'obésité a risque chez l'adulte et l'adolescent" = "Preventive and therapeutic education for diabetes and at risk obesity in adults and adolescents"), an ongoing original project in three frontier regions (Wallonia - Grand-Duchy of Luxembourg - Lorraine).
Assuntos
Atitude do Pessoal de Saúde , Cooperação do Paciente , Fidelidade a Diretrizes , Pessoal de Saúde/educação , Humanos , Educação de Pacientes como AssuntoRESUMO
The present study aimed to investigate the effects of leptin and ghrelin on pulsatile pulsatile gonadotrophin-releasing hormone (GnRH) secretion in vitro with emphasis on neuropeptide mediators and changes between prepuberty (15 days) and sexual maturity (50 days) in the male rat. When hypothalamic explants were studied 90 min after an intraperitoneal injection of leptin, ghrelin or agouti-related protein (AgRP) at 15 days, the GnRH interpulse interval (IPI) was significantly increased by ghrelin and AgRP and decreased by leptin. At 50 days, an increase in GnRH IPI was also caused by ghrelin and AgRP. When the peptides were directly incubated with the explants, the effects of leptin and AgRP in vitro were consistent with those seen after in vivo administration. By contrast, ghrelin resulted in a reduction of GnRH IPI and this was observed at 15 days only. To delineate the neuropeptide mediators of leptin and the effects of ghrelin in the hypothalamus, various hypothalamic neuropeptides and antagonists were used in vitro. At 15 days, the GnRH IPI was significantly decreased after incubation with cocaine and amphetamine-regulated transcript (CART), alpha-melanocyte-stimulating hormone, corticotrophin-releasing factor (CRF) and neuropeptide Y (NPY). The reduction of GnRH IPI caused by leptin was partially prevented by either an anti-CART antiserum or SHU 9119, a melanocortin MC3/MC4 receptor antagonist or a CRF receptor antagonist. The NPY-Y5 receptor antagonist did not influence the effects of leptin whereas that antagonist totally prevented the decrease in GnRH IPI caused by ghrelin. The ghrelin-induced reduction of GnRH IPI was partially prevented by SHU 9119. When used alone, SHU 9119 or a CRF-receptor antagonist resulted in increased GnRH IPI at 50 days while they had no effects at 15 days. The NPY-Y5 receptor antagonist resulted in increased GnRH IPI at 15 and 50 days. In conclusion, leptin and ghrelin show opposing effects on pulsatile GnRH secretion after administration in vivo whereas they both have stimulatory effects in vitro. Such effects involve consistently the anorectic peptides CART and CRF for leptin that are mainly active at 15 days. The melanocortigenic system appears to mediate the effects of both leptin and ghrelin. The effects of ghrelin also involve NPY receptors and operate effectively before and at sexual maturity.
Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Leptina/fisiologia , Hormônios Peptídicos/fisiologia , Maturidade Sexual/fisiologia , Proteína Relacionada com Agouti , Análise de Variância , Animais , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Grelina , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Masculino , Proteínas do Tecido Nervoso/metabolismo , Periodicidade , Ratos , Ratos Wistar , Receptores de Melanocortina/fisiologia , Transdução de Sinais/fisiologia , Estatísticas não ParamétricasRESUMO
Prader Willi syndrome can be viewed as a physiopathological model of obesity. Such patients deserve specific management, preferably in a multidisciplinary setting. The paper reports on 6 patients followed in the paediatric endocrine service at the University of Liege.
Assuntos
Equipe de Assistência ao Paciente , Síndrome de Prader-Willi/terapia , Criança , Humanos , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genéticaRESUMO
In higher plants and some fungi, heavy metals induce the synthesis of chelating peptides known as phytochelatins (PCs). They are characterized by the general structure (gamma-Glu-Cys)n-Gly, but in some plant species, the C-terminal glycine can be replaced by serine, glutamine, glutamate or alanine, leading to iso-phytochelatins (iso-PCs). Although the distribution of iso-PCs is considered to differ from one species to another, we previously showed that Arabidopsis thaliana (A. thaliana) cells are able to synthesize most PC-related peptides (PCs and iso-PCs) described in the literature. We also observed an accumulation of the dipeptide gamma-glutamylcysteine (gamma-EC) when cadmium (Cd) (200 microM) was added to the culture medium, suggesting that either glutathione synthetase or glycine availability could be a limiting factor for the biosynthesis of PC-related peptides. In this context, the aim of the present work was to seek new insights into the regulation of PC synthesis by performing metabolic profiling using liquid chromatography-mass spectrometry. The levels of PC-related peptides and their precursors were measured in A. thaliana cells following Cd exposure. A range of doses (0, 50, 200 and 400 microM CdNO3) and kinetic studies (from 1 to 48 h) showed a dose threshold (50 microM CdNO3) and a lag time between the appearance of PCs and iso-PCs concomitant with the gamma-EC accumulation induced by Cd, occurring at cadmium concentrations above 50 microM. This accumulation was suppressed by supplementation of the culture medium with 25 mM glycine. Glycine supplementation had a limited impact on the concentrations of glutathione and PCs whereas the levels of most iso-PCs were significantly increased. Taken together, these results indicate that GSH is involved in the biosynthesis of the iso-PCs in vivo, and that the biosynthesis of PC-related peptides is limited by the availability of glycine in the presence of high cadmium concentrations.
Assuntos
Proteínas de Arabidopsis/biossíntese , Arabidopsis/metabolismo , Glutationa/biossíntese , Metais Pesados/metabolismo , Meios de Cultura , Glutationa/química , Glutationa/metabolismo , Cinética , Nitrogênio/metabolismo , Fitoquelatinas , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Cesium as an alkali element exhibits a chemical reactivity similar to that of potassium, an essential element for plants. It has been suggested that Cs phytotoxicity might be due either to its competition with potassium to enter the plant, resulting in K starvation, or to its intracellular competition with K binding sites in cells. Such elemental interactions can be evidenced by chemical imaging, which determines the elemental distributions. In this study, the model plant Arabidopsis thaliana was exposed to 1 mM cesium in the presence (20 mM) or not of potassium. The quantitative imaging of Cs and endogenous elements (P, S, Cl, K, Ca, Mn, Fe, and Zn) was carried out using ion beam micro-chemical imaging with 5 microm spatial resolution. Chemical imaging was also evidenced by microfocused synchrotron-based X-ray fluorescence (microXRF) which presents a better lateral resolution (<1 microm) but is not quantitative. Cesium distribution was similar to potassium which suggests that Cs can compete with K binding sites in cells. Cesium and potassium were mainly concentrated in the vascular system of stems and leaves. Cs was also found in lower concentration in leaves mesophyll/epidermis. This late representing the larger proportion in mass, mesophyll/epidermis can be considered as the major storage site for cesium in A. thaliana. Trichomes were not found to accumulate cesium. Interestingly, increased Mn, Fe, and Zn concentrations were observed in leaves at high chlorosis. Mn and Fe increased more in the mesophyll than in veins, whereas zinc increased more in veins than in the mesophyll suggesting a tissue specific interaction of Cs with these trace elements homeostasis. This study illustrates the sensitivity of ion beam microprobe and microfocused synchrotron-based X-ray fluorescence to investigate concentrations and distributions of major and trace elements in plants. It also shows the suitability of these analytical imaging techniques to complement biochemical investigations of metallic stress in plants.
Assuntos
Arabidopsis/metabolismo , Césio/metabolismo , Potássio/metabolismo , Oligoelementos/metabolismo , Arabidopsis/crescimento & desenvolvimento , Césio/farmacologia , Germinação , Microscopia de FluorescênciaAssuntos
Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Adolescente , Adulto , Bélgica , Criança , Pré-Escolar , Humanos , Luxemburgo , MutaçãoRESUMO
Transcriptional regulation in response to cadmium treatment was investigated in both roots and leaves of Arabidopsis, using the whole genome CATMA microarray containing at least 24,576 independent probe sets. Arabidopsis plants were hydroponically treated with low (5 microM) or high (50 microM) cadmium concentrations during 2, 6, and 30 hours. At each time point, Cd level was determined using ICP-AES showing that both plant tissues are able to accumulate the heavy metal. RT-PCR of eight randomly selected genes confirmed the reliability of our microarray results. Analyses of response profiles demonstrate the existence of a regulatory network that differentially modulates gene expression in a tissue- and kinetic-specific manner in response to cadmium. One of the main response observed in roots was the induction of genes involved in sulfur assimilation-reduction and glutathione (GSH) metabolism. In addition, HPLC analysis of GSH and phytochelatin (PC) content shows a transient decrease of GSH after 2 and 6 h of metal treatment in roots correlated with an increase of PC contents. Altogether, our results suggest that to cope with cadmium, plants activate the sulfur assimilation pathway by increasing transcription of related genes to provide an enhanced supply of GSH for PC biosynthesis. Interestingly, in leaves an early induction of several genes encoding enzymes involved in the biosynthesis of phenylpropanoids was observed. Finally, our results provide new insights to understand the molecular mechanisms involved in transcriptional regulation in response to cadmium exposure in plants.
Assuntos
Arabidopsis/genética , Cádmio/farmacologia , Perfilação da Expressão Gênica , Genoma de Planta , Raízes de Plantas/genética , Brotos de Planta/genética , Transcrição Gênica , Arabidopsis/efeitos dos fármacos , DNA de Plantas/genética , Cinética , Análise de Sequência com Séries de Oligonucleotídeos , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.
Assuntos
Disruptores Endócrinos/efeitos adversos , Estrogênios/efeitos adversos , Puberdade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Sistema Nervoso Central/efeitos dos fármacos , Feminino , Humanos , Modelos Biológicos , Sistema Nervoso Periférico/efeitos dos fármacos , RoedoresRESUMO
The incorporation and localisation of 133Cs in a plant cellular model and the metabolic response induced were analysed as a function of external K concentration using a multidisciplinary approach. Sucrose-fed photosynthetic Arabidopsis thaliana suspension cells, grown in a K-containing or K-depleted medium, were submitted to a 1 mM Cs stress. Cell growth, strongly diminished in absence of K, was not influenced by Cs. In contrast, the chlorophyll content, affected by a Cs stress superposed to K depletion, did not vary under the sole K depletion. The uptake of Cs was monitored in vivo using 133Cs NMR spectroscopy while the final K and Cs concentrations were determined using atomic absorption spectrometry. Cs absorption rate and final concentration increased in a K-depleted external medium; in vivo NMR revealed that intracellular Cs was distributed in two kinds of compartment. Synchrotron X-ray fluorescence microscopy indicated that one could be the chloroplasts. In parallel, the cellular response to the Cs stress was analysed using proteomic and metabolic profiling. Proteins up- and down-regulated in response to Cs, in presence of K+ or not, were analysed by 2D gel electrophoresis and identified by mass spectrometry. No salient feature was detected excepting the overexpression of antioxidant enzymes, a common response of Arabidopsis cells stressed whether by Cs or by K-depletion. 13C and 31P NMR analysis of acid extracts showed that the metabolome impact of the Cs stress was also a function of the K nutrition. These analyses suggested that sugar metabolism and glycolytic fluxes were affected in a way depending upon the medium content in K+. Metabolic flux measurements using 13C labelling would be an elegant way to pursue on this line. Using our experimental system, a progressively stronger Cs stress might point out other specific responses elicited by Cs.
Assuntos
Arabidopsis/metabolismo , Radioisótopos de Césio/toxicidade , Césio/toxicidade , Potássio/farmacologia , Proteoma , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Divisão Celular/efeitos dos fármacos , Césio/farmacocinética , Radioisótopos de Césio/farmacocinética , Clorofila/metabolismo , Cinética , Espectroscopia de Ressonância MagnéticaRESUMO
The management of adolescents with diabetes mellitus involves specific aspects at diagnosis and during follow-up. A type 2 diabetes should be excluded at diagnosis since this condition is increasingly observed in closed relationhip with the progression of obesity in young people. During initial education process, the parents should be involved while a specific space and time for interaction with the adolescents is required. During follow-up, all aspects of the adolescent process should be taken into account together with diabetes. This includes risk-taking or exploratory behaviours, feeling of being different, angryness and difficulties for the adolescents to consider the long-term complication risk. Special attention should be devoted to the transition towards adult care.