A natural experiment to assess how urban interventions in lower socioeconomic areas influence health behaviors: the UrbASanté study.

BACKGROUND: Mechanisms underlying the associations between changes in the urban environment and changes in health-related outcomes are complex and their study requires specific approaches. We describe the protocol of the interdisciplinary UrbASanté study, which aims to explore how urban interventions can modify environmental exposures (built, social, and food environments; air quality; noise), health-related behaviors, and self-reported health using a natural experiment approach. METHODS: The study is based on a natural experiment design using a before/after protocol with a control group to assess changes in environmental exposures, health-risk behaviors, and self-reported health outcomes of a resident adult population before and after the implementation of a time series of urban interventions in four contiguous neighborhoods in Paris (France). The changes in environmental exposures, health-related behaviors, and self-reported health outcomes of a resident adult population will be concurrently monitored in both intervention and control areas. We will develop a mixed-method framework combining substantial fieldwork with quantitative and qualitative analytical approaches. This study will make use of (i) data relating to exposures and health-related outcomes among all participants and in subsamples and (ii) interviews with residents regarding their perceptions of their neighborhoods and with key stakeholders regarding the urban change processing, and (iii) existing geodatabases and field observations to characterize the built, social, and food environments. The data collected will be analyzed with a focus on interrelationships between environmental exposures and health-related outcomes using appropriate approaches (e.g., interrupted time series, difference-in-differences method). DISCUSSION: Relying on a natural experiment approach, the research will provide new insights regarding issues such as close collaboration with urban/local stakeholders, recruitment and follow-up of participants, identification of control and intervention areas, timing of the planned urban interventions, and comparison of subjective and objective measurements. Through the collaborative work of a consortium ensuring complementarity between researchers from different disciplines and stakeholders, the UrbASanté study will provide evidence-based guidance for designing future urban planning and public health policies. TRIAL REGISTRATION: This research was registered at the ClinicalTrial.gov (NCT05743257).

Toxic effects and bioaccumulation of carbamazepine evaluated by biomarkers measured in organisms of different trophic levels.

The antiepileptic drug carbamazapine (CBZ) readily persists in sewage-water treatment plant wastewaters and finds its way into receiving water bodies. Our study sought to examine the bioaccumulation and toxicity of CBZ using an experimental aquatic trophic chain composed of the green alga, Pseudokirchneriella subcapitata, the crustacean, Thamnocephalus platyurus, and the cnidarian, Hydra attenuata. Bioaccumulation of CBZ was estimated by liquid chromatography-tandem mass spectrometry and revealed bioaccumulation factors of 2.2 and 12.6, respectively, in algae and crustaceans. No significant bioaccumulation was observed in H. attenuata. In T. platyurus, a strong stimulation of global heme oxidase (HO) (76%), and glutathione-S-transferase activity (130%) but a drastic inhibition of cytochrome P450 3A-like activity was found which suggests alteration of enzyme activity by CBZ. However, in the hydranth H. attenuata, an increase in both global cytochrome and cytochrome P450 3A-like activity was found, while GST activity was inhibited. Lipid peroxidation was reduced in T. platyurus and H. attenuata suggesting that redox activity of the lipophilic CBZ was at play. This study highlighted the processes of carbamazepine toxicity transfer between trophic levels in aquatic organisms.

Determination of carbamazepine in aquatic organisms by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the determination of carbamazepine in microgram quantities of crustacean Thamnocephalus platyurus and the algae Pseudokirchneriella subcapitata at the ng L(-1) level. This fully validated method applied to a bioaccumulation study was found suitable for the detection of carbamazepine in small aquatic tissues.

Inactivation of the pure antiestrogen fulvestrant and other synthetic estrogen molecules by UDP-glucuronosyltransferase 1A enzymes expressed in breast tissue.

Fulvestrant (Faslodex) is administered by intramuscular injection and is converted into ketone, sulfate, sulfone and glucuronide metabolites. Glucuronidation, catalyzed by 18 members of the UDP-glucuronosyltransferase (UGT) enzyme family, plays a major role in the elimination of natural estrogens. The present study was aimed at identifying and characterizing human UGT enzymes involved in the glucuronidation of this antiestrogen as well as other synthetic estrogen derivatives with aliphatic chains on the E2 molecule. In contrast to E2, which is conjugated by UGT1A1, -1A3, -1A8, -1A10, and -2B7, fulvestrant is glucuronidated by UGT1A1, -1A3, -1A4, and -1A8. The four UGT1A-fulvestrant conjugating enzymes glucuronidate this substrate at position 3, whereas only UGT1A8 also produces fulvestrant-17-glucuronide. For E2, only UGT1A3 and UGT2B7 are capable to conjugate at 17-hydroxyposition. These observations indicate that addition of an aliphatic chain to the E2 molecule modifies the specificity of the UGT enzymes toward the C18 molecules. To further investigate the specificity of these enzymes, a series of E2 derivatives with aliphatic or phenyl chains at position 2, 7alpha, and 11beta was also tested for its conjugation with human UGT enzymes. It was observed that, in addition to UGT1A3, UGT1A1 and UGT1A8 also played important roles for the glucuronidation of these compounds. This suggests that the basic structure of E2 is one of the major determinants for the glucuronidation catalyzed by this group of enzymes. Considering the high level of UGT1A3 and -1A4 expression in the gastrointestinal tract and mammary gland, our results suggest that fulvestrant can be inactivated both in intestine and in its target tissue.