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291 results on '"Regazzoni, Luca"'

5. Using lysine adducts of human serum albumin to investigate the disposition of exogenous formaldehyde in human blood

Author

Regazzoni, Luca G, Grigoryan, Hasmik, Ji, Zhiying, Chen, Xi, Daniels, Sarah I, Huang, Deyin, Sanchez, Sylvia, Tang, Naijun, Sillé, Fenna CM, Iavarone, Anthony T, Williams, Evan R, Zhang, Luoping, and Rappaport, Stephen M

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Acetylation, Biomarkers, California, Carcinogens, Environmental, Case-Control Studies, China, Female, Formaldehyde, Humans, Inhalation Exposure, Lysine, Male, Occupational Exposure, Protein Binding, Saliva, Serum Albumin, Serum Albumin, Human, Time Factors, Adducts, Lysine 199, Blood, Formylation, Covalent modification, Environmental Science and Management, Toxicology, Pharmacology and pharmaceutical sciences, Pollution and contamination
Abstract

Formaldehyde is a human carcinogen that readily binds to nucleophiles, including proteins and DNA. To investigate whether exogenous formaldehyde produces adducts in extracellular fluids, we characterized modifications to human serum albumin (HSA) following incubation of whole blood, plasma, and saliva with formaldehyde at concentrations of 1, 10 and 100μM. The only HSA locus that showed the presence of formaldehyde modifications was Lys199. A N(6)-Lys adduct with added mass of 12Da, representing a putative intramolecular crosslink, was detected in biological fluids that had been incubated with formaldehyde but not in control fluids. An adduct representing N(6)-Lys formylation was detected in all fluids, but levels did not increase above control values over the tested range of formaldehyde concentrations. An adduct representing N(6)-Lys199 acetylation was also measured in all samples. We then applied the assay to repeated samples of human plasma from 6 nonsmoking volunteer subjects (from Berkeley, CA), and single samples of serum from 15 workers exposed to airborne formaldehyde at about 1.5ppm in a production facility and 15 control workers from Tianjin, China. Although all human plasma/serum samples contained basal levels of the products of N(6)-Lys formylation and acetylation, the putative crosslink product was not detected. Since the putative crosslink was observed in plasma incubated with formaldehyde at 1μM, this suggests that the endogenous concentration of formaldehyde in serum was much lower than reported in the literature. Furthermore, concentrations of the formyl adduct were not higher in workers exposed to formaldehyde at about 1.5ppm than in controls. Follow-up in vitro experiments with gaseous formaldehyde at 1.4ppm detected the putative crosslink in plasma but not whole blood. This combination of results suggests that N(6) formylation occurs within cells with subsequent release of adducted HSA to the systemic circulation. Comparing across human samples, levels of N(6)-Lys199 formyl adducts were present at similar concentrations in subjects from California and China (about 1mmol/mol HSA), but N(6)-Lys199 acetyl adducts were present at higher concentrations in Chinese subjects (0.34 vs. 0.13mmol/mol HSA).

Published
2017

10. A carnosine analog mitigates metabolic disorders of obesity by reducing carbonyl stress

Author

Anderson, Ethan J., Vistoli, Giulio, Katunga, Lalage A., Funai, Katsuhiko, Regazzoni, Luca, Monroe, T. Blake, Gilardoni, Ettore, Cannizzaro, Luca, Colzani, Mara, De Maddis, Danilo, Rossoni, Giuseppe, Canevotti, Renato, Gagliardi, Stefania, Carini, Marina, and Aldini, Giancarlo

Subjects
Carnosine -- Research, Metabolic diseases -- Care and treatment -- Psychological aspects, Oxidative stress -- Risk factors, Toxicity, Histidine, Skeletal muscle, Aldehydes, Insulin resistance, Exercise, Insulin, Body weight, Liver, Inflammation, Type 2 diabetes, Health care industry
Abstract

Sugar- and lipid-derived aldehydes are reactive carbonyl species (RCS) frequently used as surrogate markers of oxidative stress in obesity. A pathogenic role for RCS in metabolic diseases of obesity remains controversial, however, partly because of their highly diffuse and broad reactivity and the lack of specific RCS-scavenging therapies. Naturally occurring histidine dipeptides (e.g., anserine and carnosine) show RCS reactivity, but their therapeutic potential in humans is limited by serum carnosinases. Here, we present the rational design, characterization, and pharmacological evaluation of carnosinol, i.e., (2S)-2-(3-amino propanoylamino)-3-(1H-imidazol-5-yl)propanol, a derivative of carnosine with high oral bioavailability that is resistant to carnosinases. Carnosinol displayed a suitable ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile and was determined to have the greatest potency and selectivity toward [alpha],[beta]-unsaturated aldehydes (e.g., 4-hydroxynonenal, HNE, ACR) among all others reported thus far. In rodent models of diet-induced obesity and metabolic syndrome, carnosinol dose-dependently attenuated HNE adduct formation in liver and skeletal muscle, while simultaneously mitigating inflammation, dyslipidemia, insulin resistance, and steatohepatitis. These improvements in metabolic parameters with carnosinol were not due to changes in energy expenditure, physical activity, adiposity, or body weight. Collectively, our findings illustrate a pathogenic role for RCS in obesity-related metabolic disorders and provide validation for a promising new class of carbonyl-scavenging therapeutic compounds rationally derived from carnosine., IntroductionOvernutrition from fatty acids and complex carbohydrates is known to cause oxidative stress from multiple enzymatic and nonenzymatic sources due to the high caloric content and the prevalence of these [...]

Published
2018
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13. Economic evaluation of nitrogen reduction in RAS

Author

Regazzoni, Luca and Regazzoni, Luca

Abstract

Conventional recirculating aquaculture systems (RAS) cause significant nitrogen discharge, which can lead to eutrophication and nitrate infiltration into ground water. Furthermore, a high water exchange in the system leads to high operating costs (through the loss of salt, buffer capacity, thermal energy and discharge fees). Furthermore, more stringent regulations for discharge (as apparent from other countries) could come into play and further exacerbate discharge into recieving waters. These challenges can be alleviated using a denitrification reactor, removing the nitrate from the system water and, thus, facilitating a reduced water exchange. However, economical benefits typically outweigh the ecological incentive. Based on a mathematical model, this study aims to quantify economical benefits of the denitrification process in RAS and quantifies the reduction of emissions of three different system configurations: Scenario 1: conventional RAS (without denitrification); Scenario 2: RAS with denitrification (conventional carbon source = methanol); Scenario 3: RAS with denitrification using endogenous carbon (from system-sludge). The results of the study showed a major reduction in water exchange, buffer capacity (up to 60% reduction) and salt consumption (50 - 65%) for scenario 2 and 3. Furthermore, the potential reduction in operational expenditures for scenario 2 lays at CHF 376.- per ton of fish production and up to CHF 699.- per ton of fish production for Scenario 3.

Published
2023

14. Leitfaden Aquakulturanlagen Teil 2 : Stand der Technik zur Reduktion von Emissionen

Author

Tschudi, Fridolin, Regazzoni, Luca, Tschudi, Fridolin, and Regazzoni, Luca

Abstract

Die in einer Aquakulturanlage mit Fütterung (= intensive Aquakulturanlage) verwendete Technik beeinflusst in hohem Masse deren Emissionen in Gewässer. Je nach Produktionsmethode ist diese Technik sehr unterschiedlich, was zur Folge hat, dass eine gesetzlich geforderte Reinigung nicht einheitlich für alle Produktionsmethoden festgelegt werden kann. Im Leitfaden werden verschiedenen Intensitätsstufen der Aquakulturproduktion definiert, die massgeblichen Technologien und deren Einfluss auf die Wasserqualität aufgezeigt sowie Optimierungshilfen geboten, um die wichtigsten Emissionsparameter von Fischzuchtanlagen kosteneffizient zu reduzieren/minimieren. Das Ziel des Leitfaden «Aquakulturanlagen, Teil 2» ist es eine Hilfestellung zu bieten, um die im Leitfaden «Aquakulturanlagen, Teil 1» geforderten Massnahmen, im Rahmen der Wirtschaftlichkeit und ohne Reduktion der Produktionsmenge, erreichen zu können. Dieses Dokument soll deshalb Betreibern wie Behörden als Hilfe dienen, die Emissionen von Aquakulturanlagen wo nötig kosteneffizient reduzieren zu können.

Published
2023

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