1,721,083 research outputs found
Light for Crime Investigation
No full textThe identification and quantification of material present and collected at a crime scene, including their comparison against known standards, are critical requirements in investigative analyses. Forensic analysts use a variety of tools and techniques to achieve this. In this lecture, light is presented as one of the key elements in crime investigation. Light of selected wavelengths and instruments based on light technology are powerful tools in crime investigation (light as a “friend”) for detecting DNA, spores, polymers, fibres, glass, gunshot residues and drugs of abuse. On the other hand, light can degrade samples of utility in investigative analyses, i.e., UV light breakage of DNA during DNA profiling, and sunlight may alter crime investigation results when outdoor samples are collected and then subjected to forensic analyses (light as a “foe”). At the same time, the adverse effects of light on evidence of materials of interest could open opportunities for development of additional markers not yet explored or enrichment of libraries of dedicated instruments by adding degradation products to reduce false negative or false positive results.
Therefore, this lecture will critically review the available methods of crime scene investigation which exploit light, discussing their advantages and limitations
Meccanismi farmacologici e fotobiologici nella fototossicità da farmaco
No full textMolti farmaci, assunti per via topica o sistemica, possono aumentare la sensibilità ai raggi solari, scatenando manifestazioni cutanee di varia gravità, classificabili come reazioni fototossiche o fotoallergiche. I medicinali fotosensibilizzanti sono antibiotici di diverse classi (sulfamidici, tetracicline, chinolonici), antinfiammatori non steroidei, chemioterapici antitumorali, psicotropi (antidepressivi triciclici, neurolettici, antiepilettici, ansiolitici), antiaritmici, Ace-inibitori, diuretici, antistaminici, anestetici, antifungini e antivirali e, più recentemente, inibitori della HMG-CoA reduttasi (statine).
Tali reazioni avverse dipendono da diversi fattori, come il dosaggio del farmaco assunto, la dose e la penetrazione della radiazione attivante, lo spessore dello strato corneo, il grado di pigmentazione e la presenza degli altri cromofori a livello cutaneo, lo stato immunologico della persona interessata.
I meccanismi alla base delle reazioni di fotosensibilizzazione si distinguono in “fotodinamici” e “non fotodinamici”, a seconda che coinvolgano o meno l’ossigeno. In tutti i casi, l'assorbimento di raggi UV (principalmente UVA e UVB) produce uno stato eccitato del farmaco o di un suo metabolita, cui seguono due principali vie: una che procede attraverso la generazione di radicali liberi, in grado di danneggiare direttamente i componenti cellulari, o che possono a loro volta reagire con l’ossigeno e generare specie reattive dell’ossigeno (radicali perossidici, perossido di idrogeno, radicali ossidrilici); la seconda attraverso il trasferimento di energia o di un elettrone dal farmaco eccitato all’ossigeno con la generazione, rispettivamente, di ossigeno singoletto o di anione superossido, che, a loro volta, provocano l'ossidazione di biomolecole e quindi il danno cellulare. Farmaci fotosensibilizzanti possono anche dar luogo alla formazione di prodotti stabili di fotodegradazione, responsabili essi stessi della fototossicità in vivo. I bersagli molecolari coinvolti nelle reazioni di fotosensibilizzazione sono principalmente i lipidi, le proteine, il DNA e le membrane lisosomiali. Quando, in seguito alla modifica fotochimica delle proteine, si genera un antigene, le reazioni fotosensibilizzanti coinvolgono il sistema immunitario e sono di tipo fotoallergico, meno frequenti. Uno studio approfondito dei meccanismi farmacologici e fotobiologici di un farmaco fotosensibilizzante può essere dunque di grande utilità per prevedere tale reazione avversa anche in molecole simili e per poter prendere le opportune precauzioni per il paziente: la scelta di un farmaco non fotosensibile, in rapporto al tipo di esposizione, storia clinica, stagionalità, o la protezione dall’esposizione alle radiazioni solari, può infatti contribuire a ridurre questa reazione avversa
Photodegradation 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 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 precious biological specimen
Photolysis of cocaine, morphine, D9-tetrahydrocannabinol and EDDP in water solution.
No full textIn the frame of an ongoing project aimed at understanding the mechanisms of photodegradation and characterizing the phototoxicological profile of drugs and illicit drugs and their photosensitizing role in the biological systems [1-4], the photostability towards UVA and UVB light of cocaine, 9-tetrahydrocannabinol (THC), morphine and EDDP in water solution has been studied. The extent of photolysis and the kind of photoproducts formed have been studied by UV-Vis spectrophotometric analysis, HPLC chromatography, HRMS, and HRMS/MS analysis for accurate mass measurement of small molecules. HPLC analysis allowed us to calculate the yield of photolysis; in particular, Cocaine showed photolysis under high UV light doses, forming demethylated and hydroxylated photoproducts, and the inactive metabolite ecgonyne methyl ester, as already reported in the literature under solar irradiation and photocatalytic processes [5]. Morphine proved also to be unstable under UVB light and, in lower extent, under UVA. It forms various photoproducts, some of them corresponding to oxidation products or deriving from the addition of water to the 7,8 double bond. Also the absorption spectrum of EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), the main inactive metabolite of methadone, changes under increasing light doses, with the appearance of a new band between 300 and 350 nm. Under both UVA and UVB irradiation, it forms various degradation products, one of them dehydrogenated and another one losing also the ethyl group. For another one we suppose the loss of one of the two aromatic rings. THC also showed photolability under both UVA and UVB light. Its photodegradation products are still under investigation.
Since the photo excited drugs could photo react directly with biological substrates, produce free radicals and reactive oxygen species , or even give rise to toxic photoproducts, particularly oxidation compounds, the phototoxicological profile of illicit drugs and their photoproducts covers particular importance in the study of the toxicity/ phototoxicity of compounds in the aquatic environment
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
Effects of UVB light on antiinflammatory corticosteroids in different experimental models
No full textGlucocorticosteroids, natural hormones derived from -pregnane, are potent therapeutic agents for the treatment of a broad range of inflammatory diseases. Semisynthetic derivatives are widely used systemically mainly for the treatment of rheumatoid diseases and allergic manifestations, and many of them are effective by topical use in dermatoses and other skin diseases. This class of drugs is sensitive to UV radiation. They are a typical example of bichromophoric moiety: all possess an aliphatic ketone in the side chain linked to position 17 of the D ring, which absorbs UVB light. Ring A bears a keto group that is conjugated with either one or two double bonds, depending on the specific drug. In the former case (i.e., hydrocortisone) the chromophore is mainly sensitive to UVB. In the latter (i.e., betamethasone, fluocinolone, triamcinolone, flumethasone) both UVA and UVB effectively induce photolysis. The photodegradation of these drugs was studied in vitro (in the solid state, in organic and aqueous solutions, in commercial formulations) and ex vivo (in the pig skin). Both primary photoprocesses, cyclohexadienone ‘lumi’ rearrangement (under UV-A) and C-20 ketone homolysis (under UV-B) occur and the main photoproducts formed have been isolated and characterized. Any modification of the structure of corticosteroids, in particular the loss of the side-chain, has profound effect on their anti-inflammatory activity.
The drugs are also able to photoreact with biological substrates mainly through radical intermediates and one of them (betamethasone) shows phototoxic effects both ex vivo and in vivo (mice) too. All these results suggest to protect these drugs from light not only during storage but also after in vivo administration to avoid loss of therapeutic activity and potential phototoxic reactions
Photobehaviour and interaction with DNA of some methylpyridinium and methylquinolinium iodides
No full text- …
