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1.
Klin Padiatr ; 231(5): 262-268, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31505693

RESUMO

OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.


Assuntos
Analgésicos Opioides/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metanfetamina/toxicidade , Atividade Motora/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/psicologia , Recém-Nascido , Linguagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
2.
MMWR Morb Mortal Wkly Rep ; 68(36): 777-783, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31513558

RESUMO

Since 1999, the rate of opioid use disorder (OUD) has more than quadrupled, from 1.5 per 1,000 delivery hospitalizations to 6.5 (1), with similar increases in incidence of neonatal abstinence syndrome (NAS) observed for infants (from 2.8 per 1,000 live births to 14.4) among Medicaid-insured deliveries (2). CDC's response to the opioid crisis involves strategies to prevent opioid overdoses and related harms by building state capacity and supporting providers, health systems, and payers.* Recognizing systems gaps in provision of perinatal care and services, CDC partnered with the Association of State and Territorial Health Officials (ASTHO) to launch the Opioid Use Disorder, Maternal Outcomes, and Neonatal Abstinence Syndrome Initiative Learning Community (OMNI LC). OMNI LC supports systems change and capacity building in 12 states.† Qualitative data from participating states were analyzed to identify strategies, barriers, and facilitators for capacity building in state-defined focus areas. Most states focused on strategies to expand access to and coordination of quality services (10 of 12) or increase provider awareness and training (nine of 12). Fewer states focused on data, monitoring, and evaluation (four of 12); financing and coverage (three of 12); or ethical, legal, and social considerations (two of 12). By building capacity to strengthen health systems, state-identified strategies across all focus areas might improve the health trajectory of mothers, infants, and families affected by the U.S. opioid crisis.


Assuntos
Síndrome de Abstinência Neonatal/terapia , Transtornos Relacionados ao Uso de Opioides/terapia , Complicações na Gravidez/terapia , Efeitos Tardios da Exposição Pré-Natal/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Síndrome de Abstinência Neonatal/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Período Pós-Parto , Gravidez , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estados Unidos/epidemiologia
3.
Chem Biol Interact ; 312: 108792, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491373

RESUMO

Cadmium (Cd) is an important toxic chemical due to its increasing levels in the environment and bioaccumulation in humans and animals. The present study was performed to evaluate the effects of long-term exposure to 1, 10, or 100 µg/L Cd in drinking water on the development, reproduction and neurotoxicity of offspring when administered to mice from parental puberty to postnatal 10 weeks in offspring. The development parameters measured in offspring included physical development, reflex ontogeny, body weight and body size. The reproductive indices measured consisted of anogenital distances (AGDs), estrous cycle, sperm quality, specific gene expression in Leydig or Sertoli cells, seminiferous epithelium cycle, sex hormone levels, histological morphology and apoptosis in testis or ovary, and the levels of oxidative stress. The determination of neurotoxicity included learning and memory ability, anxiety, and related serum indicators. In addition, blood lipid level, liver and kidney function were also determined by serum biochemical assays. The results showed that exposure to Cd in the present model had no adverse effects on development, but had some reproductive toxicity and neurotoxicity, including alteration of spermatogenic epithelial staging in testis and inducing anxiety in offspring. Furthermore, the levels of total protein, globulins, total bile acid and direct bilirubin were also significantly altered, especially in female offspring. The present study suggested that long-term exposure to low doses of Cd had adverse effects on the health of the next generation, and some harmful effects showed gender differences in offspring. The present study demonstrated that attention should be paid to Cd pollution in the environment, especially before pregnancy.


Assuntos
Cádmio/toxicidade , Reprodução/efeitos dos fármacos , Animais , Análise Química do Sangue , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia
4.
An Bras Dermatol ; 94(3): 327-330, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365662

RESUMO

BACKGROUND: Seborrheic dermatitis is a common disease characterized by the erythematous plaques with oily-yellow desquamation. Increased sebaceous gland activity by androgenic hormones has played a role in the etiology of the disease. The second-to-fourth digit (2D:4D) ratio is thought to be a marker of prenatal androgen exposure. OBJECTIVES: To investigate the association between 2D:4D ratios and seborrheic dermatitis in a male population. METHODS: Healthy male controls and patients with seborrheic dermatitis were included in this study. One hundred seborrheic dermatitis patients and 120 healthy controls, aged 17-59, were enrolled. A digital Vernier caliper was used to measure the finger lengths. Seborrheic dermatitis severity was assessed using the Seborrheic Dermatitis Area and Severity Index (SDASI). RESULTS: The 2D:4D ratios of the patients (x = 0.977) were significantly lower than those of the controls (x = 1.050) for right hands (t = 6.948; p = 0.000; > 0.05). No similar relationship was found between the 2D:4D ratio for left hands (t = 0.901; p = 0.368; > 0.05). Seborrheic dermatitis severity was negatively correlated with 2D:4D ratios of right hands (r = -0.391; p = 0.000-0.05). STUDY LIMITATIONS: One of the main limitations of this study was the small sample, which got a head of us from acquiring certain findings about the 2D:4D ratio and seborrheic dermatitis. The other limitation is that the patient selection did not reflect the general population, as a single clinic was studied. CONCLUSION: To the authors' knowledge, this is the first study examining the relationship between 2D:4D ratios and seborrheic dermatitis. The result of this study may indicate a line of investigation and can support the theory of prenatal androgen exposure.


Assuntos
Dermatite Seborreica/diagnóstico , Dedos/anatomia & histologia , Adolescente , Adulto , Androgênios/metabolismo , Antropometria , Biomarcadores , Estudos de Casos e Controles , Feminino , Mãos/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Índice de Gravidade de Doença , Adulto Jovem
5.
Adv Exp Med Biol ; 1155: 415-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468419

RESUMO

Maternal dyslipidemia induces metabolic and cardiovascular disorders in adult offspring. This study tests the hypothesis that perinatal taurine supplementation prevents the adverse effects of maternal dyslipidemia on growth and cardiovascular function in adult rat offspring. Female Wistar rats were fed normal rat chow and water with (Dyslipidemia) or without dyslipidemia induction (Control) by intraperitoneal Triton WR-1339 injection, three times a week for 4 weeks. The female Control and Dyslipidemia rats were supplemented with (Control+T, Dyslipidemia+T) or without 3% taurine in water from conception to weaning. After weaning, male and female offspring were fed normal rat chow and water throughout the experiment. At 16 weeks of age, body weights significantly increased in male but not female Dyslipidemia compared to other groups, while visceral fat content significantly increased in both male and female Dyslipidemia groups. Further, both sexes displayed similar high fasting blood sugar and normal plasma leptin levels among the groups. While plasma total cholesterol and triglycerides significantly increased only in female Dyslipidemia, low-density lipoprotein cholesterol increased in both male and female Dyslipidemia groups. Mean arterial pressures and heart rates significantly increased, while baroreflex sensitivity decreased in male and female Dyslipidemia compared to all other groups. High-density lipoprotein cholesterol did not significantly different among male or female groups. These changes of the male and female Dyslipidemia group were ameliorated by perinatal taurine supplementation. The present study indicates that perinatal taurine supplementation prevents the adverse effects of maternal dyslipidemia on growth and cardiovascular function in both male and female, adult offspring.


Assuntos
Suplementos Nutricionais , Dislipidemias/fisiopatologia , Fenômenos Fisiológicos da Nutrição Materna , Taurina/farmacologia , Animais , Barorreflexo , Pressão Sanguínea , LDL-Colesterol/sangue , Feminino , Frequência Cardíaca , Lipídeos/sangue , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar
6.
Adv Exp Med Biol ; 1155: 801-819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468449

RESUMO

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance. By increasing chloride concentration through GABA-ARs, taurine serves as an effective inhibitory compound for maintaining appropriate levels of brain excitability. Considering this pharmacological mechanism of taurine facilitated inhibition through the GABA-AR, the present pilot study sought to explore the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random assignments to either solutions of Saline, Taurine, or Taurine Derived compounds (i.e., TD-101, TD-102, or TD-103) to assess the rats' responsiveness to each drug in mitigating the developmental Pb2+-exposure through the GABAergic system. Long Evans Hooded rats were assessed using an Open Field (OF) test for preliminary locomotor assessment. Approximately 24-h after the OF, the same rats were exposed to the Elevated Plus Maze (EPM) and were given an i.p. injection of 43 mg/Kg of the Saline, Taurine, or TD drugs 15-min prior to testing. Each rat was tested using the random assignment method for each pharmacological condition, which was conducted using a triple-blind procedure. The OF data revealed that locomotor activity was unaffected by Pb2+-exposure with no gender differences observed. However, Pb2+-exposure induced an anxiogenic response in the EPM, which interestingly, was ameliorated in a gender-specific manner in response to taurine and TD drugs. Female rats exhibited more anxiogenic behavior than the male rats; and as such, exhibited a greater degree of anxiety that were recovered in response to Taurine and its derivatives as a drug therapy. The results from the present psychopharmacological pilot study suggests that Taurine and its derivatives could provide useful data for further exploring the pharmacological mechanisms and actions of Taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for treating anxiety and other associated mood disorders.


Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Chumbo/efeitos adversos , Exposição Materna/efeitos adversos , Taurina/farmacologia , Animais , Feminino , Masculino , Projetos Piloto , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Distribuição Aleatória , Ratos , Ratos Long-Evans
7.
Toxicol Lett ; 315: 64-76, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419470

RESUMO

To test the hypothesis that 3-7 ring polycyclic aromatic hydrocarbons (PAHs) are responsible for the prenatal developmental toxicity (PDT) as observed with some petroleum substances (PS), the present study evaluates the PDT potency of DMSO-extracts of 7 heavy fuel oils (HFO), varying in their PAH content, and 1 highly refined base oil (HRBO), containing no aromatics, in the embryonic stem cell test (EST). All DMSO-extracts of HFO inhibit ES-D3 cell differentiation in a concentration-dependent manner and their potency is proportional to the amount of 3-7 ring PAHs they contain. All DMSO-extracts of HFOs also show aryl hydrocarbon receptor (AhR)-mediated activities, as tested in the AhR-CALUX assay. Contrarily, the HRBO-extract tested negative in both assays. Co-exposure of ES-D3 cells with selected DMSO-extracts of PS and the AhR-antagonist trimethoxyflavone, successfully counteracted the PS-induced inhibition of ES-D3 cell differentiation, confirming the role of the AhR in mediating the observed PDT of PS extracts in the EST. A good correlation exists when comparing the in-vitro with the in-vivo PDT potencies of the PS under study. Altogether, our findings corroborate the hypothesis that PS-induced PDT is caused by 3-7 ring PAHs present in these substances and that the observed PDT is partially AhR-mediated.


Assuntos
Células-Tronco Embrionárias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Petróleo/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Receptores de Hidrocarboneto Arílico/metabolismo , Bioensaio , Poluentes Ambientais/metabolismo , Feminino , Humanos , Petróleo/metabolismo , Gravidez
8.
Toxicol Lett ; 315: 87-95, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425726

RESUMO

Prenatal alcohol exposure (PAE) is often associated with congenital heart defects, most commonly septal, valvular, and great vessel defects. However, there have been no known studies on whether PAE affects the resulting fibroblast population after development, and whether this has any consequences in the postnatal period. Our previous study focused on the effects of PAE on the postnatal fibroblast population, which translated into changes in cardiac extracellular matrix (ECM) composition and cardiac function in the neonatal heart. Moreover, our lab has previously demonstrated that alcohol-induced fibrosis is mediated by oxidative stress mechanisms in adult rat hearts following chronic alcohol exposure. Thus, we hypothesize that PAE alters cardiac ECM composition that persists into the postnatal period, leading to cardiac dysfunction, and these effects are prevented by antioxidant treatment. To investigate these effects, pregnant mice were intraperitoneally injected with 2.9 g EtOH/kg body weight on gestation days 6.75 and 7.25. Controls were injected with vehicle saline. Randomly selected dams in both groups were then treated with 100 mg/kg body weight of the antioxidant N-acetylcysteine (NAC) immediately after EtOH or vehicle administration. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Ejection fraction decreased in the PAE group. NAC treatment prevented this depression of systolic function in PAE neonates. Hearts were analyzed for expression of fibroblast activation markers. Alpha smooth muscle actin (α-SMA) increased in PAE neonatal hearts, and this increase was prevented by NAC treatment. In PAE pups, collagen I decreased, but collagen III expression increased compared to saline animals; the overall collagen I/III ratio significantly decreased. When PAE mice were treated with NAC, collagen I/III ratio did not change. Overall, our data demonstrate that prenatal alcohol exposure produces changes in collagen subtype in neonatal cardiac ECM and a decline in systolic function, and these adverse effects were prevented by NAC treatment.


Assuntos
Acetilcisteína/farmacologia , Alcoolismo/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Vasos Coronários/química , Etanol/toxicidade , Fibroblastos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez
9.
Toxicol Lett ; 315: 39-46, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442585

RESUMO

The recession of regulatory T cells (Tregs) is pivotal for type 1 diabetes (T1D) progressing. Our previous study observed the decreased Tregs in prenatal nicotine exposure (PNE) offspring, but whether this led to the onset of T1D remains uncertain. Thus, this study aimed to investigate the effects of PNE on T1D susceptibility and the role of PNE-suppressed Tregs in T1D of female offspring. The decreased body weights and elevated blood glucose levels from postnatal day (PND) 21 to PND 42 indicated that PNE caused persistent impaired glucose homeostasis in offspring. The elevated serum glutamic acid decarboxylase autoantibody, the "Gold Standard" for the detection of T1D, was observed on PND 42, suggesting the early stage of T1D in PNE offspring during adolescence. The reduced pancreatic islet areas and beta cells number in PNE offspring were observed at neonatal period and became more severe during adolescence. In addition, PNE caused immune dysfunction in offspring, manifested as suppressed thymic Tregs percentage from PND 4 to PND 42 and splenic Tregs/Th17 ratio on PND 42. In conclusion, PNE resulted in metabolic changes of offspring that were consistent with T1D characteristics, which could be the consequence of Tregs recession from early life to adolescence.


Assuntos
Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/fisiopatologia , Nicotina/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Feminino , Humanos , Camundongos , Gravidez
10.
Environ Res ; 177: 108641, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421445

RESUMO

Lead (Pb) is a worldwide environmental contaminant that even at low levels influences brain development and affects neurobehavior later in life; nevertheless it is only a small fraction of the neurotoxicant (NT) exposome. Exposure to environmental Pb concurrent with other NT substances is often the norm, but their joint effects are challenging to study during early life. The aim of this review is to integrate studies of Pb-containing NT mixtures during the early life and neurodevelopment outcomes of children. The Pb-containing NT mixtures that have been most studied involve other metals (Mn, Al, Hg, Cd), metalloids (As), halogen (F), and organo-halogen pollutants. Co-occurring Pb-associated exposures during pregnancy and lactation depend on the environmental sources and the metabolism and half-life of the specific NT contaminant; but offspring neurobehavioral outcomes are also influenced by social stressors. Nevertheless, Pb-associated effects from prenatal exposure portend a continued burden on measurable neurodevelopment; they thus favor increased neurological health issues, decrements in neurobehavioral tests and reductions in the quality of life. Neurobehavioral test outcomes measured in the first 1000 days showed Pb-associated negative outcomes were frequently noticed in infants (<6 months). In older (preschool and school) children studies showed more variations in NT mixtures, children's age, and sensitivity and/or specificity of neurobehavioral tests; these variations and choice of statistical model (individual NT stressor or collective effect of mixture) may explain inconsistencies. Multiple exposures to NT mixtures in children diagnosed with 'autism spectrum disorders' (ASD) and 'attention deficit and hyperactivity disorders' (ADHD), strongly suggest a Pb-associated effect. Mixture potency (number or associated NT components and respective concentrations) and time (duration and developmental stage) of exposure often showed a measurable impact on neurodevelopment; however, net effects, reversibility and/or predictability of delays are insufficiently studied and need urgent attention. Nevertheless, neurodevelopment delays can be prevented and/or attenuated if public health policies are implemented to protect the unborn and the young child.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Lactente , Gravidez , Qualidade de Vida
11.
Environ Res ; 177: 108630, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421446

RESUMO

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8-13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8-13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8-13, 14-18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8-13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8-13, but lower odds of progressing to the next stage at 14-18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development.


Assuntos
Disruptores Endócrinos/efeitos adversos , Hormônios Esteroides Gonadais/sangue , Metais Pesados/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Maturidade Sexual , Adolescente , Teorema de Bayes , Criança , Cidades , Sulfato de Desidroepiandrosterona/sangue , Disruptores Endócrinos/urina , Estradiol/sangue , Feminino , Humanos , Inibinas/sangue , Metais Pesados/urina , México , Gravidez , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
12.
Medicine (Baltimore) ; 98(31): e16665, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374040

RESUMO

BACKGROUND: The aim of this study was to summarize current evidence evaluating the association between antenatal infection and intraventricular hemorrhage (IVH) in preterm infants. MATERIALS AND METHODS: We searched for published articles on antenatal infection and IVH in 3 English (PubMed, the Cochrane Library, and EBSCO) and 3 Chinese (VEIPU, CNKI, and WANFANG) databases on May 19, 2019. In addition, the references of these articles were screened. The included studies had to meet all of the following criteria: preterm infants (<37 weeks); comparing antenatal infection with no infection; the outcomes included IVH (all grades), mild IVH, or sereve IVH; the type of study was randomized controlled trial or cohort study. RESULTS: A total of 23 cohort studies involving 13,605 preterm infants met our inclusion criteria. Antenatal infection increased the risk of IVH (odds ratios ([OR] 2.18, 95% confidence intervals [CI] 1.58-2.99), mild IVH (OR 1.95, 95% CI 1.09-3.49) and severe IVH (OR 2.65, 95% CI 1.52-4.61). For type of antenatal infection, the ORs and 95% CI were as follows: 2.21 (1.60-3.05) for chorioamnionitis, 2.26 (1.55-3.28) for histologic chorioamnionitis, 1.88 (1.22-2.92) for clinical chorioamnionitis, and 1.88 (1.14-3.10) for ureaplasma. CONCLUSIONS: Antenatal infection may increase the risk of developing IVH in the preterm infant. The evidence base is however of low quality and well-designed studies are needed.


Assuntos
Hemorragia Cerebral Intraventricular/epidemiologia , Recém-Nascido Prematuro , Infecção/epidemiologia , Resultado da Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Peso ao Nascer , Corioamnionite/epidemiologia , Feminino , Idade Gestacional , Humanos , Gravidez , Índice de Gravidade de Doença
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(6): 718-723, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31270052

RESUMO

OBJECTIVE: To establish an improved mouse model of valproic acid (VPA)-induced autism that better mimics human autism. METHODS: We established mouse models of autism in female C57 mice by intraperitoneal injection of sodium valproate either at a single dose (600 mg/kg) on day 12.5 after conception (conventional group) or in two doses of 300 mg/kg each on days 10 and 12 after conception (modified group), and the control mice were injected with saline only on day 12.5. The responses of the mice to VPA injection, the uterus, mortality rate, and abortion rate were compared among the 3 groups. The morphology and development of the offspring mice were assessed, and their behavioral ontogeny was evaluated using 3- chambered social test, social test, juvenil play test, and open field test. RESULTS: The mortality and abortion rates were significantly lower in the modified model group than in the conventional group (P < 0.01). Compared with those in the control group, the offspring mice in both the conventional group and the modified group showed developmental disorders (P < 0.05). The mortality rate of the newborn mice was significantly lower in the modified group than in the conventional group with a rate of curvy tail of up to 100% (P < 0.001). The offspring mice in both the modified group and conventional group exhibited autism-like behavioral abnormalities, including social disorder and repetitive stereotyped behavior (P < 0.05). CONCLUSIONS: The mouse model of autism established using the modified method better mimics human autism with reduced mortality and abortion rates of the pregnant mice and also decreased mortality rate of the newborn mice.


Assuntos
Transtorno Autístico , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ácido Valproico
14.
Toxicol Lett ; 314: 18-26, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299270

RESUMO

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFß) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFß signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFß signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention.


Assuntos
Articulações/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Osteoartrite/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fatores Etários , Agrecanas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Condrogênese/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Feminino , Idade Gestacional , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulações/metabolismo , Articulações/patologia , Masculino , Exposição Materna , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Gravidez , Ratos Wistar , Fatores de Risco , Fatores Sexuais
15.
Toxicol Lett ; 314: 63-74, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31306741

RESUMO

This study aimed to verify the toxic effects of prenatal caffeine exposure (PCE) on the podocyte development in male offspring, and to explore the underlying intrauterine programming mechanisms. The pregnant rats were administered with caffeine (30 to 120 mg/kg⋅d) during gestational day (GD) 9 to 20. The male fetus on GD20 and the offspring at postnatal week (PW) 6 and PW28 were sacrificed. The results indicated that PCE caused ultrastructural abnormalities on podocyte, and inhibited the expression of podocyte marker genes such as Nephrin, Wilms tumor 1 (WT1), the histone 3 lysine 9 acetylation (H3K9ac) level in the Kruppel-like factor 4 (KLF4) promoter and its expression in the male offspring from GD20 to PW28. Meanwhile, the expression of glucocorticoid receptor (GR) and histone deacetylase 7 (HDAC7) in the fetus were increased by PCE. In vitro, corticosterone increased GR and HDAC7 whereas reduced the H3K9ac level of KLF4 and KLF4/Nephrin expression. KLF4 over-expression reversed the reduction of Nephrin expression, knockdown of HDAC7 and GR antagonist RU486 partially reversed the inhibitory effects of corticosterone on H3K9ac level and KLF4 expression. In conclusion, PCE caused podocyte developmental toxicity in male offspring, which was associated with corticosterone-induced low-functional programming of KLF4 through GR/HDAC7/H3K9ac pathway.


Assuntos
Cafeína/toxicidade , Estimulantes do Sistema Nervoso Central/toxicidade , Histonas/metabolismo , Nefropatias/induzido quimicamente , Fatores de Transcrição Kruppel-Like/metabolismo , Podócitos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Acetilação , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Idade Gestacional , Glucocorticoides/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Nefropatias/embriologia , Nefropatias/genética , Nefropatias/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Lisina , Masculino , Exposição Materna , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fenótipo , Podócitos/metabolismo , Podócitos/ultraestrutura , Gravidez , Regiões Promotoras Genéticas , Ratos Wistar , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Pneumologie ; 73(7): 407-429, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31291669

RESUMO

The third part of the DGP statement introduces the current body of knowledge on less studied health outcomes associated with exposure to ambient air pollution: the negative impact on metabolism leading to impaired glucose tolerance and diabetes as well as contribution to the development of neurodegenerative disorders and delayed cognitive function in children. Furthermore, prenatal exposure and adverse effects on mother and child are addressed. Finally, the currently discussed biological mechanisms underlying various health effects associated with exposure to air pollution are described.Differing, but often complementary biological mechanisms create the basis for the diverse health outcomes caused by air pollution. Oxidative stress and a subclinical inflammatory response in the lungs and on a systemic level ("low-grade systemic inflammation") are considered to be key mechanisms. They promote secondary alterations in the body, such as vascular or metabolic processes, and may also result in the currently studied epigenetic phenomena or neuroinflammation. In this context, the health significance of soluble particulate matter and the role of ultrafine particles translocated across biological membranes into blood vessel and transported via the circulation to secondary target organs, such as liver, brain or the fetus, are intensively discussed.Diabetes is one of the leading chronic diseases worldwide, with a prevalence of almost 14 % in Germany. Although lifestyle factors are the main causes, current evidence suggests that long-term exposure to air pollution may additionally increase the risk for type 2 diabetes. Supporting evidence for a causal role of air pollution is provided by studies addressing the regulation of the blood glucose levels in metabolically healthy participants, insulin sensitivity, or pregnancy-related diabetes. Experimental studies provide further support for plausible biological mechanisms. However, prospective studies are needed to gain more evidence, taking multiple lifestyle and environmental factors, such as green space and noise, and an improved individual exposure assessment into account.The aging population has an increased risk of neurodegenerative diseases. First studies point towards a contribution of chronic exposure to air pollution, specifically by particulate matter. Several studies report its association with decreased neurocognitive capacity or an increased prevalence of dementia or Alzheimer's disease in adults. However, the studies are inhomogeneous regarding design, exposure and outcome, leading to inconsistent results. With respect to the influence on neurocognitive development of children, first studies suggest an association between the level of air pollution, e. g. at school, and delayed cognitive development.Even though the evidence for the different biological endpoints during pregnancy is still heterogeneous, the studies generally point towards an adverse impact of air pollution on the maternal and fetal organisms. The strongest evidence exists for low birth weight, with small effect sizes of only some grams, and for a higher incidence of reduced birth weight (< 2500 g). An increased risk for gestational hypertension and preeclampsia underscores the possible impact of exposure to air pollution on the maternal organism. However, the current body of evidence does not yet allow a final conclusion on the influence of intrauterine exposure to air pollution regarding early childhood lung function and development of allergies, particularly in light of the fact that it is hard to distinguish in epidemiological studies between the effects of pre- and postnatal exposure.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental , Material Particulado/efeitos adversos , Resultado da Gravidez/epidemiologia , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Estudos Prospectivos
17.
Toxicol Lett ; 314: 98-105, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31348986

RESUMO

Parental exposure to cigarette smoke is closely related to the development of long-term metabolic diseases in the offspring. However, different exposure times at various developmental stages may cause these effects to vary. In this study, mice were exposed to cigarette smoke condensate (CSC) during the developmental time stages of paternal puberty or/and maternal pregnancy. The results showed that either paternal or maternal exposure to CSC could lead to increased low birth weight (LBW) and fetal growth restriction (FGR) of the offspring, but maternal factors were the leading ones. Moreover, maternal exposure during pregnancy could induce lipid metabolism abnormalities in the adulthood offspring. Most importantly, additional paternal CSC exposure further induced diabetes in adolescent offspring who experienced altered weight gain, blood lipids, and glucose metabolism. A preliminary analysis indicated that the offspring with metabolic abnormalities also had significant changes in their intestinal microbiota. In conclusion, this study showed that parental CSC exposure has an impact on the metabolic properties of the offspring, and multiple parental exposures to adverse factors may significantly increase the risk of long-term metabolic abnormalities.


Assuntos
Glicemia/metabolismo , Fumar Cigarros/efeitos adversos , Diabetes Mellitus/etiologia , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Fumaça/efeitos adversos , Fatores Etários , Animais , Biomarcadores/sangue , Peso ao Nascer , Diabetes Mellitus/sangue , Feminino , Retardo do Crescimento Fetal/etiologia , Microbioma Gastrointestinal , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Gravidez , Medição de Risco , Fatores de Risco
18.
Dev Neuropsychol ; 44(5): 429-442, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31353953

RESUMO

Prenatal cocaine exposure (PCE) has ramifications for feedback processing. Measuring neural oscillatory dynamics (during electroencephalography) provides insight into the time signatures and neural processes of feedback processing in adolescents with PCE. We measured spectral power in alpha and theta frequency bands while 49 adolescents with PCE and 34 non-drug exposed (NDE) performed a task with win/no-win feedback. Compared to NDE individuals, those with PCE showed reduced alpha power and increased theta power in response to no-win feedback. These findings suggest altered reactivity in PCE adolescents.


Assuntos
Ritmo alfa , Ritmo beta , Cocaína/efeitos adversos , Retroalimentação Psicológica/fisiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Adolescente , Eletroencefalografia , Feminino , Humanos , Masculino , Gravidez
19.
Life Sci ; 233: 116689, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31348949

RESUMO

BACKGROUND: Maternal metabolic syndrome during gestation and lactation leads to several Se-status-related metabolic changes in offspring. MS leads to hepatomegaly, liver oxidation, resistance to insulin challenges and selenoptroteins expression upregulation, producing an energy imbalance in hepatocytes. As Se is necessary for correct heart function, Se deposits are depleted and selenoproteins expression downregulated in heart; this depletion being related to cardiovascular damage. Recently, selenoproteins have been directly implicated in the central endocrine regulation of appetite and energy homeostasis. METHODS: To obtain information about how Se is involved in regulating endocrine peripheral energy balance during MS process, two experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65% and Se: 0.1 ppm). At the end of lactation (21d old), the pups' appetite profile, tissular Se deposits and peptides from gastrointestinal tract (including pancreas), leptin, skeletal growth markers and cytokines in serum were measured. RESULTS: MS-exposed pups present changes in Se homeostasis, appetite profile and endocrine energy balance signals related to impaired insulin secretion and high leptin serum values. This profoundly affects the pups' growth profile since muscle and bones are in catabolic process and brown adipose tissue (BAT) mass decreases. CONCLUSION: These results indicate that the pups are suffering a process similar to diabetes type 1 which appeared when dams received low Se dietary supply and they point to Se as an important marker and key treatment for these disorders during gestation and lactation that affect future adult health.


Assuntos
Doenças do Sistema Endócrino/etiologia , Metabolismo Energético/efeitos dos fármacos , Desenvolvimento Fetal/efeitos dos fármacos , Síndrome Metabólica/complicações , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Selênio/administração & dosagem , Animais , Biomarcadores/sangue , Doenças do Sistema Endócrino/patologia , Feminino , Homeostase , Resistência à Insulina , Leptina/sangue , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Síndrome Metabólica/tratamento farmacológico , Estresse Oxidativo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Ratos Wistar , Selênio/efeitos adversos , Selênio/sangue
20.
BMJ ; 366: l4151, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292120

RESUMO

OBJECTIVE: To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood. DESIGN: Retrospective cohort study. SETTING: Population based birth registry linked with health administrative databases in the province of Ontario, Canada. PARTICIPANTS: All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes. MAIN OUTCOME MEASURES: Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding. RESULTS: Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups. CONCLUSIONS: No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.


Assuntos
Saúde da Criança , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal , Adulto , Asma/epidemiologia , Pré-Escolar , Feminino , Gastroenteropatias/epidemiologia , Humanos , Lactente , Recém-Nascido , Infecção/epidemiologia , Ontário/epidemiologia , Gravidez , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
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