Direct Effects, Compensation, and Recovery in Female Fathead Minnows Exposed to a Model Aromatase Inhibitor

BackgroundSeveral chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis.ObjectivesThe objective of this study was to provide a detailed characterization of molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole (FAD).MethodsFish were exposed via water to 0, 3, or 30 microg FAD/L for 8 days and then held in clean water for 8 days, with samples collected at four time points during each 8-day period. We quantified ex vivo steroid production, plasma steroids, and plasma vitellogenin (Vtg) concentrations and analyzed relative transcript abundance of 10 key regulatory genes in ovaries and 3 in pituitary tissue by real-time polymerase chain reaction.ResultsEx vivo 17beta-estradiol (E2) production and plasma E2 and Vtg concentrations were significantly reduced after a single day of exposure to 3 microg or 30 microg FAD/L. However, plasma E2 concentrations recovered by the eighth day of exposure in the 3-microg/L group and within 1 day of cessation of exposure in the 30-microg/L group, indicating concentration- and time-dependent physiologic compensation and recovery. Concentration-dependent increases in transcripts coding for aromatase (A isoform), cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, and follicle-stimulating hormone receptor all coincided with increased E2 production and recovery of plasma E2 concentrations.ConclusionsResults of this research highlight the need to consider compensation/adaptation and recovery when developing and interpreting short-term bioassays or biomarkers or when trying to predict the effects of chemical exposures based on mode of action

Representation Contracts

Tematika ovoga rada vezana je uz određene ugovore građanskog prava, odnosno konkretno ugovor o nalogu, ugovor o komisiji i ugovor o punovlašću. Nalog kao temelj svakog ugovora o zastupanju predstavlja određeni odnos nalogodavca prema nalogoprimcu kojim se nalogoprimac obvezuje na ispunjenje nalogom određenih poslova prema trećim osobama. Nalog kao takav nije vezan samo isključivo uz ugovor o nalogu, već je i dio, odnosno temelj ugovora o komisiji i ugovora o punovlašću. Za svaki od navedenih ugovora se može reći da postoje dva pravna odnosa i to odnos između nalogodavca i nalogoprimatelja, odnosno komisionara i komitenta, te opunomoćitelja i opunomoćenika, kao i vanjski odnos između treće osobe s kojom se sklapa pravni posao i osobe koja zastupa nalogodavatelja. Razlika između navedenih ugovora postoji, te kako je navedeno u Zakonu o obveznim odnosima, ali i drugoj literaturi, nalogoprimatelj temeljem ugovora o nalogu nastupa za račun nalogodavca, za razliku od njega komisionar nastupa u svoje ime, a za račun komitenta pri obavljanju poslova, dok će opunomoćenik biti obvezan u ime i za račun zastupanoga sklapati određene pravne poslove.The paper addresses certain civil law contracts, more precisely the mandate contract, commission contract and representation contract. The commission as the basis of each representation contract represents an interrelation between the principal and the contractor, which binds the contractor to carry out certain orders for the third party. The commission as such is not exclusively related to the mandate contract. It is also a part or the basis of the commission contract and the representation contract. For each of the above mentioned contracts one can argue that there are two legal relationships: that between the principal and the contractor, i.e. the commissioner and the client on the one hand, and the giver of authorization and the assignee on the other, as well as the external relationship between the third party with whom the legal transaction is concluded and the person representing the principal. There is a difference between the specified contracts, as it is stated in the Civil Obligations Act and other references as well. The contractor acts on behalf of the principal on the basis of the mandate contract. Unlike him, the commissioner acts in his own name and on behalf of the client when operating, whereas the assignee is obligated to conclude certain legal transactions in the name and on behalf of the represented person

Nužna obrana

Kako bi se moglo govoriti o nužnoj obrani, kao temi ovoga rada, najprije je potrebno obrazložiti obilježja kaznenog djela, odnosno protupravnost kao jedno od obilježja iz koje i proizlazi nužna obrana, kao mogućnost isključenja protupravnosti. S obzirom na određenje Kaznenog zakona Republike Hrvatske razlikujemo kao isključenje protupravnosti nužnu obranu i krajnju nuždu. Nužna obrana je ona obrana koja je prijeko potrebna da počinitelj od sebe ili drugoga odbije istodobni ili izravno predstojeći protupravan napad. Pravo na nužnu obranu izvodi se iz dva načela, odnosno, načela samozaštite prema kome nitko nije dužan trpjeti povrede svojih pravnih dobara pa je ovlašten silom odbiti napad na njih i načela potvrđivanja, odnosno afirmacije prava, jer pravni poredak može postojati samo ondje gdje dominira pravo nad nepravom. Slijedeće pri obradi teme nužne obrane su njezini elementi koji se odnose na napad i obranu koji moraju imati određene značajke da bi bili pravno relevantni

Nužna obrana

Kako bi se moglo govoriti o nužnoj obrani, kao temi ovoga rada, najprije je potrebno obrazložiti obilježja kaznenog djela, odnosno protupravnost kao jedno od obilježja iz koje i proizlazi nužna obrana, kao mogućnost isključenja protupravnosti. S obzirom na određenje Kaznenog zakona Republike Hrvatske razlikujemo kao isključenje protupravnosti nužnu obranu i krajnju nuždu. Nužna obrana je ona obrana koja je prijeko potrebna da počinitelj od sebe ili drugoga odbije istodobni ili izravno predstojeći protupravan napad. Pravo na nužnu obranu izvodi se iz dva načela, odnosno, načela samozaštite prema kome nitko nije dužan trpjeti povrede svojih pravnih dobara pa je ovlašten silom odbiti napad na njih i načela potvrđivanja, odnosno afirmacije prava, jer pravni poredak može postojati samo ondje gdje dominira pravo nad nepravom. Slijedeće pri obradi teme nužne obrane su njezini elementi koji se odnose na napad i obranu koji moraju imati određene značajke da bi bili pravno relevantni

Assessment of river sediment toxicity: combining empirical zebrafish embryotoxicity testing with in silico toxicity characterization

Quantitative chemical analyses of 428 organic contaminants (OCs) indicated the presence of 313 OCs in the sediment extracts from Sava River, Croatia. Pharmaceuticals were present in higher concentrations than pesticides thus confirming their increasing threat to freshwater ecosystems. Toxicity evaluation of the sediment extracts from four locations (Jesenice, Rugvica, Galdovo and Lukavec) using zebrafish embryotoxicity test (ZET) accompanied with semi-quantitative histopathological analyses exhibited correlation with cumulative number and concentrations of OCs at the investigated sites (10.05, 15.22, 1.25, and 9.13 µg/g respectively). Toxicity of sediment extracts and sediment was predicted using Toxic unit (TU) approach and persistence, bioaccumulation and toxicity (PBT) ranking. Additionally, influential OCs and genes were identified by graph mining of the prior knowledge informed, site-specific chemical-gene interaction models. Predicted toxicity of sediment extracts (TUext) was similar to the results obtained by ZET and associated histopathology with Rugvica sediment being the most toxic, followed by Jesenice, Lukavec and Galdovo. Sediment TU (TUsed) favoured OCs with low octanol-water partition coefficients like herbicide glyphosate and antibiotics ciprofloxacin and sulfamethazine thus indicating locations containing higher concentrations of these OCs (Galdovo and Rugvica) as the most toxic. Results suggest that comprehensive in silico sediment toxicity predictions advocate providing equal attention to organic contaminants with either very low or very high log Kow

Photochemical mobilization of dissolved hydrocarbon oxidation products from petroleum contaminated soil into a shallow aquifer activate human nuclear receptors

Elevated non-volatile dissolved organic carbon (NVDOC) concentrations in groundwater (GW) monitoring wells under oil-contaminated hydrophobic soils originating from a pipeline rupture at the National Crude Oil Spill & Natural Attenuation Research Site near Bemidji, MN are documented. We hypothesized the elevated NVDOC is comprised of water-soluble photooxidation products transported from the surface to the aquifer. We use field and laboratory samples in combination with complementary analytical methods to test this hypothesis and determine the biological response to these products. Observations from optical spectroscopy and ultrahigh-resolution mass spectrometry reveal a significant correlation between the chemical composition of NVDOC leached from photochemically weathered soils and GW monitoring wells with high NVDOC concentrations measured in the aquifer beneath the contaminated soil. Conversely, the chemical composition from the uncontaminated soil photoleachate matches the NVDOC observed in the uncontaminated wells. Contaminated GW and photodissolution leachates from contaminated soil activated biological targets indicative of xenobiotic metabolism and exhibited potential for adverse effects. Newly formed hydrocarbon oxidation products (HOPs) from fresh oil could be distinguished from those downgradient. This study illustrates another pathway for dissolved HOPs to infiltrate GW and potentially affect human health and the environment