51 research outputs found
Effect of a negative regulatory element (NRE) on the human CYP1A1 gene expression in breast carcinoma MCF-7 and hepatoma HepG2 cells
AbstractThe expression of the cytochrome P4501A1 gene, CYP1A1, is induced by e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) mainly by transcriptional mechanisms. The inducers mediate their effect upon binding and activation of the aryl hydrocarbon receptor (AHR) transcription-factor complex. Utilizing chimeric CYP1A1/HCAT constructs transient gene expression experiments indicate that the putative negative regulatory element (NRE) of CYP1A1 influence the relative TCDD induced CAT activity in HepG2 cells, whereas this effect was not observed in MCF-7 cells. Differences in the formation of cell-specific protein-DNA complexes were demonstrated by gel retardation assays suggesting a functional difference of NRE in these two cell lines
DIAGNOSIS OF ENDOCRINE DISEASE: Steroid Hormone Analysis in Diagnosis and Treatment of DSD Position Paper of EU COST Action BM 1303 "DSDnet".
Disorders or differences in sex development (DSD) comprise a heterogeneous group of conditions with an atypical sex development. For optimal diagnosis highly specialized laboratory analyses are required across European countries. Working group 3 of EU COST (European Cooperation in Science and Technology) Action BM 1303 "DSDnet" "Harmonisation of Laboratory Assessment" has developed recommendations on laboratory assessment for DSD regarding the use of technologies and analytes to be investigated. This position paper on steroid hormone analysis in diagnosis and treatment of DSD was compiled by a group of specialists in DSD and/or hormonal analysis, either from participating European Countries or international partner countries. The topics discussed comprised analytical methods (immunoassay/mass spectrometry based methods), matrices (urine/serum/saliva) and harmonisation of laboratory tests. The following positions were agreed upon: Support of the appropriate use of immunoassay and mass spectrometry based methods for diagnosis and monitoring of DSD. Serum/plasma and urine are established matrices for analysis. Laboratories performing analyses for DSD need to operate within a quality framework and actively engage in harmonisation processes so that results and their interpretation are the same irrespective of the laboratory they are performed in. Participation in activities of peer comparison such as sample exchange or when available subscribing to a relevant external quality assurance program should be achieved. The ultimate aim of the guidelines is the implementation of clinical standards for diagnosis and appropriate treatment of DSD to achieve the best outcome for patients, no matter where patients are investigated or managed
Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain
The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative
microenvironment in adipose tissue. This study was conducted in a subsample (n=144) of the GraMo cohort
(Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were
quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted
for potential confounders.
Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx)
activity [exp(β)=1.20, p=0.060] and decreased levels of reduced glutathione (GSH) [exp(β)=0.55,
p=0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione
reductase (GRd) activity [exp(β)=0.83, exp(β)=0.72, respectively], and BPA was borderline associated
to increased levels of oxidized glutathione (GSSG) [exp(β)=1.73, p-value=0.062]. MeP was inversely
associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of
thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79].
Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the
activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as
a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.This research was supported
in part by research grants from the European Union Commission
(H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research
Networking Center-CIBER de EpidemiologĂa y Salud PĂşblica
(CIBERESP), from the Institute of Health Carlos III, supported by
European Regional Development Fund/FEDER (FIS-PI13/02406, FISPI14/
00067, FIS-PI16/01820, FIS-PI16/01812, FIS-PI16/01858 and
FIS-PI17/01743), and from the ConsejerĂa de Salud, Junta de AndalucĂa
(PS-0506-2016). Funding for the equipment used was provided by
Velux Fonden, Augustinus Fonden and Svend Andersen Fonden. The
authors thank Kirsten og Freddy Johansens Fond and the International
Centre for Research and Research Training in Endocrine Disruption of
Male Reproduction and Child Health (EDMaRC, Rigshospitalet,
Copenhagen University) for economic support. Dr. Juan Pedro Arrebola
is under contract within RamĂłn y Cajal Program (Ministerio de
EconomĂa, Industria y Competitividad de España, RYC-2016-20155)
Fatal encephalopathy after an isolated overdose of cocaine
Cocaine induced brain damage can be divided into primary neurotoxic effects causing toxic encephalopathy, secondary effects of compromised cerebral blood flow in ischaemic and haemorrhagic stroke, cerebral vasculitis and vasospasm, and tertiary effects due to hypoxia as a result of cardiopulmonary collapse. Toxic leucoencephalopathy mainly affects white matter (WM) tracts serving higher cerebral function, thereby leading to altered personality, attention deficits and memory impairment in mild cases and to dementia, coma and brain death in severe cases. Here we describe the case of a 21-year-old man who committed suicide by injecting cocaine. The cocaine induced a toxic leucoencephalopathy, which was proven at autopsy
Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats
Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs
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