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Understanding the behavioral pathways of xenobiotics in the environment allows for the assessment of the risk to humans resulting from their presence. The aim of the study was to assess whether photo-induced degradation of cefazolin is linked to phototoxic effects on living cells. Cefazolin solutions were exposed to UV-Vis radiation, and then quantitative analysis was performed using the validated UPLC-MS/MS method. The obtained data indicate that the photodegradation of cefazolin proceeds according to first-order kinetics and results in the formation of four main products. To understand the environmental modification on the toxicity of cefazolin and its photodegradation products to human health, we used a human skin culture and animal models. Both in vitro and in vivo studies help assess not only the toxicity of the original drug but also the potential ecological risks posed by its degradants. Considering the potential species-specific ecotoxicity of products for biota, it was necessary to use a set of organisms representing different trophic levels. The bioindication tests using Thamnocephalus platyurus and Daphnia magna as test organisms have shown similar EC50 values after 48 h of incubation (≈40 µg/mL). The luminescence inhibition test (LumiMara), based on the measurement of luminescence quenching of saltwater and freshwater bacterial strains, showed increased toxicity of the tested mixtures obtained during irradiation at different time. The highest toxicity was observed for saltwater strains #2 Photobacterium phosphoreum (NCIMB 30267) for all irradiated solutions (MTC=0.030 µg/mL, after 8 h exposure), whereas in the case of non-irradiated solutions it was freshwater strain #11 Photorhabdus asymbiotica (NCIMB 30276), showing the lowest MTC values (12.913 µg/mL). In vivo studies have shown that cefazolin and its photodegradation products have a pronounced effect on the development, motility and cardiac function of Zebrafish larvae, which is manifested by increased mortality (by approx. 10 % for a concentration of 1 µg/mL; 2 h), body deformations (by approx. 0–10 % for a concentration 10 µg/mL and by 0 ̶ 20 % for 50 µg/mL compared to the control), and changes in heart rate (slowing of the heart rate by approx. 5–15 bpm noticeable with longer irradiation times, i.e. 6 and 8 h). Similarly, in vitro cytotoxicity studies using a cell proliferation assay showed increased cytotoxicity of the mixtures obtained after the longest exposure period compared to the non-irradiated antibiotic. The experimental results are consistent with the in silico data, which indicate increased toxicity of photodegradants, especially their cardiotoxic and cytotoxic potential. The performed analyses clearly indicate a higher toxicity of the tested mixtures compared to pure cefazolin in relation to living organisms. [Display omitted] • 3 R principles used in ecotoxicity testing to minimize the use of animals. • Increased ecotoxicity of cefazolin's photodegradation products. • Bioindication tests shown increased mixtures toxicity at different irradiation time. • Increased mortality, deformities, changes in heart rate were observed in Zebrafish. [ABSTRACT FROM AUTHOR]

Purpose: The purpose was to evaluate quality of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) myocardial scans and its correlation with background glucose (BG) after simplified 5% intravenous glucose load protocol. Methods: An intravenous glucose load protocol was applied in 69 normoglycemic patients with confirmed coronary artery disease. The blood glucose level was measured every 15 min. Results: Eighty-four percent of images were optimal, 8.7% suboptimal, and 7.3% uninterpretable. The quality of 18F-FDG-PET was BG independent and body mass index dependent (P= .0007). Conclusions: Simplified glucose load protocol is a safe and efficient method of preparation for FDG cardiac viability study in patients with normoglycemia. [ABSTRACT FROM AUTHOR]

An important problem is the impact of photodegradation on product toxicity in biological tests, which may be complex and context-dependent. Previous studies have described the pharmacology of cefepime, but the toxicological effects of its photodegradation products remain largely unknown. Therefore, photodegradation studies were undertaken in conditions similar to those occurring in biological systems in silico , in vitro , in vivo and ecotoxicological experiments. The structures of four cefepime photodegradation products were determined by UPLC-MS/MS method. The calculated in silico ADMET profile indicates that carcinogenic potential is expected for compounds CP-1, cefepime, CP-2 and CP-3. The Cell Line Cytomotovity Predictor 2.0 tool was used to predict the cytotoxic effects of cefepime and related compounds in non-transformed and cancer cell lines. The results indicate that possible actions include: non-small cell lung cancer, breast adenocarcinoma, prostate cancer and papillary renal cell carcinoma. OPERA models were used to predict absorption, distribution, metabolism and excretion (ADME) endpoints, and potential bioactivity of CP-2, cefepime and CP-4. The results obtained in silico show that after 96h of exposure, cefepime, CP-1, CP-2, and CP-3 are moderately toxic in the zebrafish model, while CP-4 is highly toxic. On the contrary, cefepime is more toxic to T. platyurus (highly toxic) compared to the zebrafish model, similar to products CP-4, CP-3 and CP-2. In vitro cytotoxicity studies were performed by MTT assay and in vivo acute embryo toxicity studies using Danio rerio embryos and larvae. In vitro showed an increase in the cytotoxicity of products with the longest exposure period i.e. for 8 h. Additionally, at a concentration of 200 μg/mL, statistically significant changes in metabolic activity were observed depending on the irradiation time. In vivo studies conducted with Zebrafish showed that both cefepime and its photodegradation products have only low toxicity. Assessment of potential ecotoxicity included Microbiotests on invertebrates (Thamnotoxkit F and Daphtoxkit F), and luminescence inhibition tests (LumiMara). The observed toxicity of the tested solutions towards both Thamnocephalus platyurus and Daphnia magna indicates that the parent substance (unexposed) has lower toxicity, which increases during irradiation. The acute toxicity (Lumi Mara) of nonirradiated cefepime solution is low for all tested strains (<10%), but mixtures of cefepime and its photoproducts showed growth inhibition against all tested strains (except #6, Photobacterium phoreum). Generally, it can be concluded that after UV–Vis irradiation, the mixture of cefepime phototransformation products shows a significant increase in toxicity. [Display omitted] • Pharmaceuticals may pose a potential threat to the natural environment. • The impact of drug photodegradation on ecotoxicity is extremely important. • Phototransformation yield products that are more/less toxic than the parent compound. • Studies related to ecological risk assessment must be the subject of continuous research. [ABSTRACT FROM AUTHOR]