321 research outputs found
Drug- photosensitised modifications of proteins
No full textSeveral topical or systemic drugs may result in some photosensitivity reactions under light exposure. Wavelengths within the UV-A (320-400 nm) range are more likely to cause drug-induced photosensitization, although occasionally UV-B (290-320 nm) can also be responsible for such effects. Proteins are one of the main biological targets of this damage. The mechanisms involved in chemical changes of amino acids and proteins upon irradiation are mediated by radicals (Type I), drug-derived peroxides, singlet oxygen (Type II) and direct binding (Type III), giving rise to drug-protein photoadducts with nucleophilic aminoacids (e.g., serine, tyrosine, lysine), protein photocross-linking (drug-protein or protein-protein), photodegradation or photooxidation of aminoacids (e.g., tryptophan, tyrosine, cysteine/cystine, phenilalanine). The photosensitised modification of proteins and enzymes could lead to loss of their biological functions with damage to some organs and the occurrence of phototoxic side effects as well as to photoallergic reactions when the immune system is involved in the skin. Phenothiazines (fluphenazine, chlorpromazine, promethazine), non selective NSAIDs (tiaprophenic acid) and Coxibs (celecoxib), Diuretics (hydrochlorothiazide), 5-fluorouracil, Corticosteroids (fluocinolone, flumethasone), chlorochresol, are examples of pharmaceutical compounds able to induce protein modifications under UV irradiation.
References:
H. Alenius, D. W. Roberts, Y.Tokura, A. Lauerma, G. Patlewicz and M. S. Roberts, Skin, drug and chemical reactions Drug Discovery Today: Disease Mechanisms, Vol. 5, No.2, e211-e220 (2008)
Miranda M.A. J.V. Castell, D. Hernandez et al., Drug-Photosensitized Protein Modification: Identification of the Reactive Sites and Elucidation Of Reaction Mechanisms with Tiaprofenic Acid/Albumin as Model System Chem.Res. Toxicol., 11, 172-177 (1998)
Miranda M.A. J.V. Castell, D. Hernandez et al., Mechanisms of Photosensitizion by Drugs: Involvement of Tyrosines in the Photomodification of Proteins Mediated by Tiaprofenic Acid In Vitro, Toxicol. In Vitro, 11 , 653-659 (1997)
Caffieri S., Miolo G., Seraglia S., Dalzoppo D., Toma F.M., van Henegouwen G.M., Photoaddition of fluphenazine to nucleophiles in peptides and proteins. Possible cause of immune system side effects, Chem. Res. Toxicol., 20, 1470-6 (2007
Evaluation of the antiviral activity of psoralens. G. Miolo, R. Tomanin, A. De Rossi, F. Dall'Acqua, F. Zacchello, M. Scarpa.
No full textPhotodegradation of Drugs of Abuse in Hair
No full textHair analysis is a valuable tool in clinical and forensic toxicology to demonstrate drug exposure when cases of chronic intoxication, use, abuse, or single dose consumption need to be diagnosed in the context of facilitated crimes, withdrawal controls, doping controls, or workplace drug testing, with a large window from weeks to months/years for drug detection. However, scalp hair is exposed to sunlight and/or artificial light for many hours per day; hence, the action of light on hair could alter the content of drugs/illicit drugs and/or metabolites and the xenobiotics can gradually disappear from the hair shaft or be transformed into other compounds having a different structure from the parent molecule. Thus, light exposure should be considered as a potential confounder in studies investigating xenobiotics in hair giving rise to reduced drug concentrations or even false negative results. On the other hand, the formation of new photodegradation products could lead to the identification of new markers of abuse useful in forensic evaluations. Although the importance of the potentially detrimental effect of light on the exogenous molecules present in the hair shaft is being recognized, very few studies are actually present in the literature about the photodecomposition of illicit drugs in this valuable biological specimen
Photostability and Phototoxicity of Hydrocortisone acetate
No full textHydrocortisone acetate is a corticosteroid used systemically for the treatment of rheumatoid arthritis, endocrine disorders and allergic diseases, and topically for dermatoses as an antiinflammatory and antiallergic agent.
Its sensitivity to UV light has been studied. Hydrocortisone is rather stable under UVA light (2.5% and 1.5% lysis in PBS and in MeOH, respectively, under 30 J/cm2), but it readily decomposes under 15 J/cm2 of UVB light (70% in PBS, 57% in MeOH, 40% in the solid state and 20% in a commercially available cream).
Two main photoproducts have been isolated and characterized. They correspond to the 18 and 18-CH3 diastereoisomers formed by loss of 17--ketol side chain (necessary for glucocorticoid activity) followed by the 17-OH oxidation to keto-group. Moreover, Hydrocortisone showed photohemolytic properties under UVB light, partly dependent on the presence of oxygen and mostly on the radical species and stable photoproducts formed during irradiation. No phototoxicity was found under UVA light.
Therefore, hydrocortisone acetate must be protected from light during storage and administration to avoid both the phototoxic effects and the reduction of therapeutic activity
Betamethasone: photolysis and phototoxicity
No full textThe photolysis of Betamethasone (1), a synthetic glucocorticosteoid used for the treatment of rheumatic diseases and dermatologic disorders, has been studied both in organic and aqueous solution under UVA and UVB light. The drug decomposes up to 90 % under UVB light (18 J/cm2) and to 40 % under UVA light (30 J/cm2). Four main photoproducts have been isolated by TLC and characterized by NMR and MS analyses. They correspond to: 1a , the byciclo[3.1.0]hex-3-en-2-one rearranged derivative; 1b, the 1,11-oxysteroid derivative ; 1c, the 17-H derivative (formed by loss of 17 –OH) ; 1d, the 17 keto derivative, generated from a Norrish Type I reaction .
Bethametasone also shows photosensitizing properties: it is able to induce photohemolysis under UVB (95 %, 1,5 J/cm2) and UVA light (55 %, 30 J/cm2). The isolated photoproducts also photohemolyze the RBC in the order of potency: 1c > 1a > 1b > 1d, thus proving to contribute to the overall photosensitizing properties of Betamethasone.
The photostability of the drug was also studied in the solid state and in different pharmaceutical formulations. The presence of additives (such as sodium metabisulphite, phenol) have some photoprotective effect but they do not completely preserve the drug from photolysis.
Therefore, both the loss of therapeutic activity and toxicity may be induced when Betamethasone is exposed to light
“Il cost management dei servizi: logiche, strumenti e prospettive di ricerca”
No full textIl tema dei servizi pervade la nostra economia e costituisce un aspetto di crescente rilevanza sia a livellomacroeconomico che di management dell’impresa. L’impiego dell’ICT ha radicalmente innovato il mododi produrre, di competere (network) e di rapportarsi con il mercato, contribuendo allo sviluppo di modellidi business e prodotti nuovi caratterizzati da un elevato contenuto di conoscenza. I beni fisici costituisconosempre di più un sistema di conoscenze “congelate” in attesa di utilizzazione e la creazione di valoreavviene mediante un processo di co-produzione con i clienti, nel quale le risorse intangibili (knowledge)assumono un ruolo fondamentale (Normann, 2001; Vargo e Lusch, 2004). Con la crescita di rilevanza e dicomplessità che i servizi ed i relativi business model hanno assunto e stanno assumendo, sorge con forzal’esigenza di sistemi di controllo per misurare e gestire le relative performance, in termini tradizionali dicosti, qualità, tempo, innovazione e secondo logiche ancora inesplorate. Il saggio intende affrontare il temadella gestione di costi e performance nei servizi nella prospettiva di trasformazione dei modelli di businessin precedenza delineata svolgendo in prima istanza una review della letteratura italiana e straniera,considerando sia i contributi teorici, sia quelli empirici. Lo scopo del saggio è inoltre quello di evidenziarele particolarità ed i problemi della determinazione e della gestione dei costi dei servizi, le logiche e glistrumenti di cost management coerenti con tali particolarità, nonché le pratiche più diffuse. In questo modol’analisi svolta predispone le condizioni per un’analisi sul ruolo del cost management nell’ambito deisistemi di misurazione/gestione delle performance dei servizi ed evidenzia i gap di conoscenza sui qualiconcentrare i futuri sforzi di ricerca riproponendo anche l’interrogativo se sia possibile una teoria generaledei costi di produzione (Coda, 1968).[...
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