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1.
Cell ; 167(3): 843-857.e14, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27720451

RESUMO

Glucagon and thyroid hormone (T3) exhibit therapeutic potential for metabolic disease but also exhibit undesired effects. We achieved synergistic effects of these two hormones and mitigation of their adverse effects by engineering chemical conjugates enabling delivery of both activities within one precisely targeted molecule. Coordinated glucagon and T3 actions synergize to correct hyperlipidemia, steatohepatitis, atherosclerosis, glucose intolerance, and obesity in metabolically compromised mice. We demonstrate that each hormonal constituent mutually enriches cellular processes in hepatocytes and adipocytes via enhanced hepatic cholesterol metabolism and white fat browning. Synchronized signaling driven by glucagon and T3 reciprocally minimizes the inherent harmful effects of each hormone. Liver-directed T3 action offsets the diabetogenic liability of glucagon, and glucagon-mediated delivery spares the cardiovascular system from adverse T3 action. Our findings support the therapeutic utility of integrating these hormones into a single molecular entity that offers unique potential for treatment of obesity, type 2 diabetes, and cardiovascular disease.


Assuntos
Glucagon/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Tri-Iodotironina/efeitos dos fármacos , Animais , Aterosclerose/tratamento farmacológico , Peso Corporal/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Engenharia Química/métodos , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Sinergismo Farmacológico , Glucagon/efeitos adversos , Glucagon/química , Glucagon/farmacologia , Hiperglicemia/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Terapia de Alvo Molecular , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Tri-Iodotironina/efeitos adversos , Tri-Iodotironina/química , Tri-Iodotironina/farmacologia
2.
Ecotoxicology ; 33(1): 47-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38182932

RESUMO

This study provides evidence of fine-grained genetic structuring in Mediterranean mussels (Mytilus galloprovincialis) from the Strait of Istanbul, caused by barriers to gene flow via contaminant-mediated selection. In this study, mitochondrial D-loop sequences were analyzed in mussels from 8 localities, all less than 30 kilometers apart, with differing contaminant loads. The results were: 1) Intra-population genetic differentiation (ΦST) between sites with high and low contaminant loads was high (up to 0.459), even at distances of only a few kilometers. 2) Genetic diversity was negatively correlated with the contaminant load ("genetic erosion"). 3) There was evidence of selection, based on haplotype frequencies and neutrality tests (Tajima's D), with purifying selection at the most contaminated site and balancing selection at the least contaminated. 4) Genetic distance was not correlated with geographic distance (no isolation-by-distance), but was correlated with contaminant load at each site. 5) Population dendrograms and Bayesian estimators of migration indicated that gene flow between sites was affected by contamination. For the dendrograms of the sampling sites, the clades clustered according to contaminant load more than geographic distance. Overall, these results suggest that 1) contamination may serve as a genotype-dependent dispersal barrier (i.e., contamination may not affect total number of migrants, just the relative proportions of the haplotypes in the established immigrants), leading strong population differentiation over short distances, and 2) genetic erosion may occur by a combination of selection and altered patterns of haplotype-specific gene flow. These effects may be more pronounced in the Strait of Istanbul than in other locations because of the riverine nature and strong, uni-directional current of the strait.


Assuntos
Fluxo Gênico , Mytilus , Animais , Teorema de Bayes , Mytilus/genética , Haplótipos , Alimentos Marinhos , Variação Genética , Genética Populacional
3.
Arch Toxicol ; 96(1): 335-365, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34687351

RESUMO

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.


Assuntos
Transtorno Autístico , Retardadores de Chama , Neuropeptídeos , Animais , Feminino , Éteres Difenil Halogenados/toxicidade , Humanos , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo
4.
Diabetologia ; 63(6): 1236-1247, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32140744

RESUMO

AIMS/HYPOTHESIS: Treatment with the α3ß4 nicotinic acetylcholine receptor (nAChR) agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), improves glucose tolerance in diet-induced obese (DIO) mice, but the physiological and molecular mechanisms are unknown. METHODS: DMPP (10 mg/kg body weight, s.c.) was administered either in a single injection (acute) or daily for up to 14 days (chronic) in DIO wild-type (WT) and Chrnb4 knockout (KO) mice and glucose tolerance, tissue-specific tracer-based glucose metabolism, and insulin signalling were assessed. RESULTS: In WT mice, but not in Chrnb4 KO mice, single acute treatment with DMPP induced transient hyperglycaemia, which was accompanied by high plasma adrenaline (epinephrine) levels, upregulated hepatic gluconeogenic genes, and decreased hepatic glycogen content. In contrast to these acute effects, chronic DMPP treatment in WT mice elicited improvements in glucose tolerance already evident after three consecutive days of DMPP treatment. After seven days of DMPP treatment, glucose tolerance was markedly improved, also in comparison with mice that were pair-fed to DMPP-treated mice. The glycaemic benefit of chronic DMPP was absent in Chrnb4 KO mice. Chronic DMPP increased insulin-stimulated glucose clearance into brown adipose tissue (+69%), heart (+93%), gastrocnemius muscle (+74%) and quadriceps muscle (+59%), with no effect in white adipose tissues. After chronic DMPP treatment, plasma adrenaline levels did not increase following an injection with DMPP. In glucose-stimulated skeletal muscle, we detected a decreased phosphorylation of the inhibitory Ser640 phosphorylation site on glycogen synthase and a congruent increase in glycogen accumulation following chronic DMPP treatment. CONCLUSIONS/INTERPRETATION: Our data suggest that DMPP acutely induces adrenaline release and hepatic glycogenolysis, while chronic DMPP-mediated activation of ß4-containing nAChRs improves peripheral insulin sensitivity independently of changes in body weight via mechanisms that could involve increased non-oxidative glucose disposal into skeletal muscle.


Assuntos
Obesidade/tratamento farmacológico , Obesidade/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Glicemia/efeitos dos fármacos , Catecolaminas/metabolismo , Iodeto de Dimetilfenilpiperazina/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Knockout , Agonistas Nicotínicos/uso terapêutico
5.
Environ Sci Technol ; 54(2): 1111-1119, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31867966

RESUMO

Epidemiological studies have indicated the thyroid-disrupting effects of persistent organic pollutants (POPs). However, the association of low-exposure POPs with thyroid hormones (THs) remains unclear. Here, we aim to assess the association of low exposure of POPs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated dibenzo-p-dioxins and furans, with THs [total L-thyroxine (TT4), total 3,3',5-triiodo-L-thyronine (TT3), and total 3,3',5'-triiodo-L-thyronine (TrT3)] measured in human breast milk. Ninety-nine breast milk samples were collected from the LUPE cohort (2015-2016, Bavaria, Germany). Fourteen PBDEs, 17 PCBs, and 5 PCDD/Fs had quantification rates of >80%. Nonmonotonic associations were observed. In adjusted single-pollutant models, (1) TT4 was inversely associated with BDE-99, -154, and -196; (2) TT3 was inversely associated with BDE-47, -99, -100, -197, -203, -207, and OCDD; and (3) TrT3 was inversely associated with BDE-47, -99, -183, and -203. Multipollutant analysis using principal component analysis and hierarchical clustering revealed inverse associations of PBDEs (BDE-28, -47, -99, -100, -154, -183, and -197) with TT4 and TrT3. These results indicate that POPs at low levels might be related to reduced THs. This study shows that human breast milk might be an appropriate specimen to evaluate the thyroid disruption of POPs.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animais , Dibenzofuranos , Feminino , Alemanha , Éteres Difenil Halogenados , Homeostase , Humanos , Leite Humano , Hormônios Tireóideos
6.
J Environ Sci Health B ; 55(8): 694-703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536292

RESUMO

Organochlorine pesticides (OCPs) were analyzed in three different ages (half-, 1.5-, 2.5-year-old) for needles and semi permeable membrane devices (SPMDs) at three deployment periods from sea level to 1881 meter above sea level. Individual HCHs concentrations ranged between 1.4 and 129 pg/g fw depending on the age and sampling season while 2.5-year-old needles showed higher HCHs levels compared to half and 1.5- year-old. Correlation between elevation and HCH concentration in SPMDs was found but not in needle samples. Concentrations of HCHs in SPMDs indicated clearly cold condensation effect on accumulation in winter period and increased with altitude. Concentrations of DDTs in half and 1.5-year-old needles were lower than 2.5-year-old needles. The highest total concentration of DDTs was detected in 1-year-period SPMD. Higher concentrations were found in 2.5-year-old needles for other OCPs. Seasonal and altitude-dependent changes were not observed for other OCPs in SMPDs. Total accumulation of OCPs in SPMDs were found higher than in needles. On the contrary, an increased accumulation rate was observed for HCHs in SPMD. In general, Total concentrations of DDTs and HCHs were similar to total of other OCPs in all altitudes when dominating endosulfan wasnot taken into account in the computation of total concentration of other OCPs.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/instrumentação , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Altitude , Monitoramento Ambiental/métodos , Pinus/química , Estações do Ano , Turquia
7.
Biomed Chromatogr ; 32(4)2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29166705

RESUMO

Monoamines, acting as hormones and neurotransmitters, play a critical role in multiple physiological processes ranging from cognitive function and mood to sympathetic nervous system activity, fight-or-flight response and glucose homeostasis. In addition to brain and blood, monoamines are abundant in several tissues, and dysfunction in their synthesis or signaling is associated with various pathological conditions. It was our goal to develop a method to detect these compounds in peripheral murine tissues. In this study, we employed a high-performance liquid chromatography method using electrochemical detection that allows not only detection of catecholamines but also a detailed analysis of nine monoamines and metabolites in murine tissues. Simple tissue extraction procedures were optimized for muscle (gastrocnemius, extensor digitorum longus and soleus), liver, pancreas and white adipose tissue in the range of weight 10-200 mg. The system allowed a limit of detection between 0.625 and 2.5 pg µL-1 for monoamine analytes and their metabolites, including dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, epinephrine, 3-methoxy-4-hydroxyphenylglycol, serotonin and 5-hydroxyindoleacetic acid. Typical concentrations for different monoamines and their metabolization products in these tissues are presented for C57Bl/6 J mice fed a high-fat diet.


Assuntos
Monoaminas Biogênicas/análise , Monoaminas Biogênicas/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Técnicas Eletroquímicas/métodos , Tecido Adiposo Branco/química , Animais , Monoaminas Biogênicas/química , Dieta Hiperlipídica , Sistema Digestório/química , Hipotálamo/química , Limite de Detecção , Modelos Lineares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/química , Especificidade de Órgãos , Reprodutibilidade dos Testes
8.
Environ Monit Assess ; 189(11): 543, 2017 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-28988385

RESUMO

Performance reference compounds (PRCs) are neutral organic compounds, introduced in a passive sampler prior deployment for the assessment of in situ sampling rate. In this study, evaluation of in situ sampling rates of 16 13C-PAH-PRCs with moderate and high hydrophobicity was established to provide an overall correction factor for variations in virtual organism (VO) uptake rates of the analytes of interest. In situ sampling rate was compared to an empirical model during sampling campaign in 2011 with VO in 12 different sites along the Three Gorges Reservoir (TGR) in China. A discrepancy was observed for high hydrophobic compounds with log K ow ranging from 5.18 to 6.63 where ΣPAH concentration in TGR from Huckins model (305,624 pg/L) was resulted to be roughly 2-fold higher than the alternative procedure (182,292 pg/L). A relationship between in situ sampling rates of the 16 13C-PAH-PRCs (Rs, PRC ) and log K ow was set up to allow then calculation of analyte sampling rate Rs analyte (N) of various organic pollutants with log K ow  ≤ 6.63.


Assuntos
Monitoramento Ambiental/instrumentação , Modelos Químicos , Compostos Orgânicos/química , Poluentes Químicos da Água/análise , China , Interações Hidrofóbicas e Hidrofílicas , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/química , Água/química , Poluentes Químicos da Água/química
9.
Environ Monit Assess ; 188(6): 352, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27188302

RESUMO

In the present work, the concentration of eight metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn) was determined in the sediments and transplanted and native mussels (Mytilus galloprovincialis). The study was conducted in Turkish marinas, shipyards, and shipbreaking yards. The effect of metal pollution was evaluated by determining the levels of metallothionein (MT) in the mussels. The extent of contamination for each single metal was assessed by using the geoaccumulation index (I geo) and enrichment factor (EF). Whereas, to evaluate the overall metal pollution and effect, the pollution load index (PLI), modified contamination degree (mC d), potential toxicity response index (RI), mean effects range median (ERM) quotient (m-ERM-Q), and mean PEL quotient (m-PEL-Q) were calculated. The influence of different background values on the calculations was discussed. The results indicated a significant metal pollution caused by Cu, Pb, and Zn especially in shipyard and shipbreaking sites. Higher concentrations of MT were observed in the ship/breaking yard samples after the transplantation.


Assuntos
Bivalves/efeitos dos fármacos , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Metalotioneína/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise , Animais , Bivalves/metabolismo , Turquia
10.
Environ Health ; 14: 19, 2015 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-25888735

RESUMO

BACKGROUND: Environmental pollutant exposure may play certain roles in the pathogenesis and progression of diabetes mellitus including gestational diabetes mellitus (GDM). We hypothesize that heavy metal exposure may trigger GDM during pregnancy. The objective of this study was to investigate the possible associations between selected heavy metal exposure and GDM risk. METHODS: This investigation is a retrospective case-control study nested within a cohort of 1359 pregnant women. These participants were recruited in Xiamen Maternity and Child Care Hospital, China, during June to July, 2012. All their newborns' meconium samples were collected. By reviewing the antenatal care records, 166 GDM mothers were screened out from the 1359 participants; 137 of 166 GDM mothers offered their newborns' meconium samples for the metal analysis. Those 137 mothers were set as the case group. Similarly, 294 healthy mothers without any gestational complication were initially screened out from the rest 1193 non-GDM mothers. 190 of the 294 healthy mothers offered their newborns' meconium samples for the metal analysis. Those 190 mothers were set as the control group. Arsenic (As), mercury (Hg), lead (Pb), cadmium (Cd), and chromium (Cr) levels in these case-control meconium samples were measured by inductively coupled plasma mass spectrometry. The possible association between the metal levels and maternal GDM risk of studied subjects was assessed by binary logistic regression. RESULTS: GDM prevalence of 12.21% was observed in the investigated 1359 participants. The concentrations of As, Hg, Cr and Cd in studied cases were significantly higher (p < 0.05) than those of controls. After adjustments for maternal age, pre-pregnant body mass index, gravidity, parity, hepatitis B virus infection, and newborn sex, As, Cd and Cr were found to be positively associated with GDM prevalence in dose-dependent manners. Among them, As was detected in all samples and its levels associated the maternal GDM with the adjusted odds ratios of 3.28 [95% CI 1.24, 8.71], 3.35 [95% CI 1.28, 8.75] and 5.25 [95% CI 1.99, 13.86] for the 2(nd), 3(rd) and 4(th) quartiles, respectively. CONCLUSIONS: The present work implies that exposure to some of the selected metals (noticeably As) may contribute to maternal GDM risk during pregnancy.


Assuntos
Arsênio/toxicidade , Diabetes Gestacional/epidemiologia , Exposição Materna , Mecônio/química , Metais Pesados/toxicidade , Adulto , Estudos de Casos e Controles , China/epidemiologia , Diabetes Gestacional/induzido quimicamente , Feminino , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Medição de Risco , Adulto Jovem
11.
Environ Monit Assess ; 187(3): 132, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25701473

RESUMO

The human body is not a chemically uncontaminated system. Every simple action that humans undertake, such as drinking water, eating, nursing, and even breathing air, puts the system under environmental xenobiotic exposure stress. Environmental chemicals have been shown to produce unwanted effects on health and remove the right to healthy living, starting from the first encounter in utero to geriatrics, throughout the lifespan. Organochlorine pesticides (OCPs) and polychlorinated biphenyl (PCB) levels, important members of the persistent organic pollutants (POPs), have been detected before in human breast milk and also in the adipose tissue of women from different regions of Turkey; however, there was no information about the blood levels of these chemicals. This study generated the first information that evaluates OCP and PCB contamination levels in the blood of the women living in Turkey. The current study measured the blood concentrations of OCPs and PCBs in 58 healthy women (age 20-41 years; mean age 28 years) who were living in Istanbul, Turkey, in the years 2010-2012. Samples were analyzed for 29 OCPs and 18 PCB congeners using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). PCB 153 was the predominant congener (643.2 pg/g lipid), followed by PCB 138 and PCB 180. 4,4'-DDE (24872.8 pg/g lipid) was the most common organochlorinated pesticide contaminant in studied blood samples. Results for analyzed chlorinated compounds were as follows: ∑PCB 2682 ± 3300 pg/g lipid; ∑DDT 25,938 ± 28,644 pg/g lipid; and ∑HCH 2930 ± 2222 pg/g lipid, respectively. The mean concentration of ∑WHOPCB-TEQ was 0.037 pg/g on a lipid basis. This information will be important base data during the assessment of the general health concerns of women, as well as for studies about how endocrine disruptors affect humans for forthcoming studies.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Bifenilos Policlorados/sangue , Tecido Adiposo , Adulto , Ar/análise , Aleitamento Materno , Disruptores Endócrinos/análise , Disruptores Endócrinos/sangue , Exposição Ambiental/análise , Monitoramento Ambiental , Poluentes Ambientais/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Halogenação , Substâncias Perigosas/análise , Humanos , Hidrocarbonetos Clorados/análise , Lipídeos/análise , Praguicidas/análise , Bifenilos Policlorados/análise , Turquia
12.
Environ Health ; 13(1): 8, 2014 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-24524244

RESUMO

BACKGROUND: Exposomics is the cutting-edge concept of screening the environmental risk factors for disease. In the novel "top-down" approach, we estimate the molecular exposome by measuring all body fluid analytes in a case-controlled study. However, to detect diverse pollutants, a sufficient sample size and multiple analytical methods are required. This may lead to dramatically increased costs and research workload. METHODS: To help reduce complexity, we suggest a sample pooling strategy along with a scheme for combining both general unknown or multi-targeted screening with targeted analysis. The sample pooling method was tested using computer simulations. RESULTS: By comprehensively analysis of pooled samples, it is possible to identify environmental risk factors. Factors are initially screened in the pooled case and control population samples, then in the randomized grouped and pooled case and control subpopulation samples. In the sample grouping, five or more pools were suggested for groups having 30 individuals per pool. CONCLUSIONS: This study suggests that sample pooling is a useful strategy for exposomics research, which provides a hypothesis-free method for pollutant risk screening.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/metabolismo , Metabolômica , Projetos de Pesquisa , Estudos de Casos e Controles , Simulação por Computador , Exposição Ambiental/efeitos adversos , Humanos , Medição de Risco/métodos
13.
Ecotoxicol Environ Saf ; 105: 29-35, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24780230

RESUMO

Human health and the health of the environment have entwined. In this paper we underpin this position by presenting a modeling approach named CombiSimilarity, which has been developed by the first author in the software tool PyHasse comprising a wide variety of partial ordering tools. A case study of 18 Organochlorine Pesticides (OCPs) detected in soil as well as in human breast milk samples in the Taurus Mountains in Turkey is carried out. Seven soil samples and 44 breast milk samples were measured. We seek to answer the question whether the contamination pattern in breast milk is associated with the contamination pattern in soil by studying the mutual quantitative relationships of the chemicals involved. We could demonstrate that there is a similarity with respect to the concentration profiles between the soil and breast milk pollution. Therefore the hypothesis may be formulated that the concentrations of chemicals in the milk samples are strongly related to the soil contamination. This supports the concept that soil could be a surrogate for human exposure at background locations.


Assuntos
Interpretação Estatística de Dados , Monitoramento Ambiental/métodos , Hidrocarbonetos Clorados/análise , Leite Humano/química , Poluentes do Solo/análise , Solo/química , Humanos , Modelos Estatísticos
14.
Altern Lab Anim ; 42(1): 71-80, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24773490

RESUMO

The increase in commercial production and inevitable release of fullerenes into the environment accelerates concerns about their potential toxicity. Furthermore, the concomitant release of xenobiotics poses a health hazard to humans, and might present potential long-term risks to human health. In the present study, we found that an aqueous suspension of buckminsterfullerene (aqu-nC60) does not result in the induction of ethoxyresorufin-O-deethylase (EROD) activity in H4IIE rat liver cells in vitro. The simultaneous and sequential exposure of aqu-nC60 and the dioxin TCDD induces EROD activity to the same extent as TCDD alone (i.e. in the absence of fullerene), in spite of the high affinity of C60 for TCDD. However, the co-exposure of aqu-nC60 and PCB 126 induces elevated EROD activity, and sequential exposure increases responses 2-fold compared to the control samples. Our in vitro observations suggest a potential source of drug-drug type interaction of fullerene with xenobiotics, particularly after a sequential exposure.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Fulerenos/farmacologia , Bifenilos Policlorados/farmacologia , Dibenzodioxinas Policloradas/farmacologia , Animais , Células Cultivadas , Interações Medicamentosas , Indução Enzimática/efeitos dos fármacos , Tamanho da Partícula , Ratos , Suspensões
15.
Anal Bioanal Chem ; 405(16): 5571-82, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23657445

RESUMO

Catecholamines play essential roles in several physiological processes in vertebrates as well as in invertebrates. While several studies have shown the presence of these substances in surface water invertebrates, their occurrence in groundwater fauna is unproven. In the present study, the presence of different catecholamines (i.e., noradrenaline, adrenaline, and dopamine) in individual specimens of groundwater amphipods of the genus Niphargus (mostly Niphargus inopinatus) was investigated via two independent analytical methods: HPLC/EcD and UPLC/TOF-MS. Mean values for catecholamine levels were 533 pg mg(-1) fresh weight for noradrenaline, 314 pg mg(-1) for adrenaline, and 16.4 ng mg(-1) for dopamine. The optimized protocol allowed the detection of CAs in single organisms of less than 1 mg fresh weight. Catecholamine concentration patterns in groundwater invertebrates are briefly discussed here with respect to their evolutionary adaptation to an environmentally stable, energy-poor habitat.


Assuntos
Anfípodes/metabolismo , Catecolaminas/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Animais , Calibragem , Dopamina/análise , Epinefrina/análise , Água Subterrânea , Norepinefrina/análise
16.
Gen Comp Endocrinol ; 194: 110-7, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24055559

RESUMO

Temperature stress in invertebrates is known to be reflected by changes in catecholamine levels. However, the mechanisms of stress response are not fully understood. Groundwater and surface water amphipods are expected to be differently adapted to temperature elevations due to the different temperature regimes in their habitats and consequently, show a different stress response. No data have been published so far regarding the effects of stress on catecholamine patterns in groundwater invertebrates and accordingly, comparisons with surface water fauna are also missing. In this study, we compared the average catecholamine levels in two taxonomically related amphipod species: Niphargus inopinatus, living in groundwater with constant water temperatures throughout the year, and Gammarus pulex, a surface water stream amphipod frequently exposed to diurnal and seasonal temperature fluctuations. Furthermore, we tracked the immediate changes in whole-animal catecholamine levels in response to heat stress in both species. Pronounced differences in the catecholamine levels of the two species became apparent, with the average dopamine (DA) level of N. inopinatus being almost 1000 times higher than that in G. pulex. The noradrenaline (NA) concentrations in N. inopinatus were on average two orders of magnitude higher than in G. pulex, and for adrenaline (A), the difference constituted one order of magnitude. When exposed to short-term heat stress, both species showed a response in terms of catecholamine levels, but the observed patterns were different. In N. inopinatus, temperature stress was reflected by the appearance of adrenaline, while in G. pulex a significant increase in noradrenaline levels occurred in the treatment with the highest temperature elevation.


Assuntos
Anfípodes/efeitos dos fármacos , Catecolaminas/metabolismo , Anfípodes/fisiologia , Animais , Dopamina/química , Água Subterrânea , Temperatura
17.
Int J Environ Health Res ; 23(3): 226-46, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22963053

RESUMO

Exposure data to organochlorine pesticides (OCPs) of mothers' breast milk samples were measured in different locations in the Taurus Mountains/Turkey. Villages at five altitudes were looked upon. The data analysis method applied is the Hasse diagram technique, based on Discrete Mathematics. For each of the five regions, one Hasse diagram was calculated and showed the same maximal object, namely, p-p'-Dichlorodiphenyldichloroethane (DDE). In a further data investigation step, we performed the similarity analyses of the locations in order to quantify the similarities and incomparabilities. It was revealed that no correlation exists between most altitudes and the pattern of contamination of breast milk samples. The two lowest situated areas, Sahil at sea level and Ciftlikköy at 121 m above sea level were similar. We reduced the datasets by applying the interval analysis followed by similarity analyses. We observed that endrin (END1), mirex (MIRE), and pentachlorobenzene (PECB) reduce most severely the similarity.


Assuntos
Hidrocarbonetos Clorados/isolamento & purificação , Leite Humano/química , Resíduos de Praguicidas/isolamento & purificação , Altitude , Exposição Ambiental , Monitoramento Ambiental , Poluentes Ambientais/isolamento & purificação , Feminino , Humanos , Modelos Teóricos , Turquia
18.
Artigo em Inglês | MEDLINE | ID: mdl-23705610

RESUMO

Titanium dioxide (TiO2) nanoparticles have a high surface-to-mass ratio and rapidly aggregate in water causing great difficulties for toxicity test exposed to aquatic organisms or other cell lines. This study uses a cell viability kit for routine toxicity test of TiO2 as well as other nanoparticles which accumulate in the aquatic environment. Tetrahymena immediately endocytoses TiO2 nanoparticles and stores them in food vacuoles until the particles undergo exocytosis as larger aggregates. However, during the process of endocytosis and exocytosis, TiO2 particles interfere with cell growth and consequently induce acute toxicity. It exerted high cell growth inhibition at 20 h incubation and induces significant cytotoxic effects. Surprisingly, the effect of TiO2 decreases at 40 h incubation, due to the recovery of cell growth and reduction of the cytotoxicity of the particles.


Assuntos
Nanopartículas/toxicidade , Tetrahymena/crescimento & desenvolvimento , Titânio/toxicidade , Testes de Toxicidade/métodos , Nanopartículas/química
19.
Artigo em Inglês | MEDLINE | ID: mdl-23573924

RESUMO

In this study, Mediterranean mussel species, Mytilus galloprovincialis, were exposed to phenanthrene (PHE) due to its ubiquitousness and bioavailability in the aquatic environment. Kinetic parameters of the PHE bioaccumulation and depuration were calculated for an 11-day uptake and subsequent 11-day depuration periods. Those values of kinetic rate constants for uptake and depuration of PHE were calculated as varying between 93-177 and 0.18-0.25, respectively. Negative correlation was observed between the PHE concentrations and kinetic rate constants. Bioaccumulation Factors (BAFs) for the mussels exposed to different PHE concentrations were calculated from both kinetic rate constants and from the experimental data and found between 509-701 and 441-658, respectively. Experimental quantitative structure activity relationship (QSAR) values for PHE were found comparable to the calculated QSARs reported in literature. Two sub-lethal biomarker methods (filtration rate and lysosomal stability) were applied to observe the responses of the mussels throughout the experimental period. Results of both biomarkers show that PHE negatively affects mussels during the uptake of PHE, and mussels were able to recover physiologically at the end of depuration period according to the filtration rate results.


Assuntos
Mytilus/metabolismo , Fenantrenos/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Biomarcadores , Cromatografia Gasosa-Espectrometria de Massas , Cinética , Lisossomos/metabolismo , Mytilus/efeitos dos fármacos , Fenantrenos/sangue , Fenantrenos/metabolismo , Espectrometria de Fluorescência , Turquia , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/metabolismo
20.
Environ Monit Assess ; 185(3): 2723-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22797882

RESUMO

This study reports evidence of increased chlorpyrifos contamination in sediment and water in Lake Naivasha following its intensive application in the horticultural farms in the catchment area. Analytical results show that levels of chlorpyrifos residues were influenced by climate-induced rainfall pattern with higher levels reported during period of heavy precipitation with significant decrease during low rainfall. On average, the levels ranged between 14.8 and 32.8 ng g(-1) in sediment during rainy season compared to a range of 8.5-16.6 ng g(-1) in the dry season. Additionally, the mean concentration of chlorpyrifos in water ranged between 8.61 and 22.4 µg L(-1) during rainy season and below detection limit (bdl) -13.6 µg L(-1) in dry season as quantified by enzyme-linked immunosorbent assay. Meanwhile, independent t test analysis indicated that there was significant difference in concentration at p ≤ 0.05 between the seasons with respect to sediment and water samples. This demonstrated that climate-induced variations had considerable influence on contamination. While diazinon and carbofuran were equally applied intensively, their levels were below the detection limit in the all the samples analyzed. ELISA results were validated by the capillary-HPLC photodiode-array detector instrument analysis, and statistical comparison showed no significant difference between them. It was evident that chlorpyrifos residues determination in water and sediment by ELISA can be a useful strategy in environmental management and monitoring program, and a complimentary analytical tool to high performance liquid chromatography. Levels of chlorpyrifos detected in sediment and water were found to exceed recommended criteria for protection of aquatic life and preservation of water quality and may be hazardous if not regularly monitored.


Assuntos
Mudança Climática , Sedimentos Geológicos/química , Lagos/química , Resíduos de Praguicidas/análise , Poluentes Químicos da Água/análise , Clorpirifos/análise , Monitoramento Ambiental , Ensaio de Imunoadsorção Enzimática , Quênia , Medição de Risco
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