A Direct Aqueous Derivatization GSMS Method for Determining Benzoylecgonine Concentrations in Human Urine

A sensitive and reliable method for extraction and quantification of benzoylecgonine (BZE) and cocaine (COC) in urine is presented. Propyl-chloroformate was used as derivatizing agent, and it was directly added to the urine sample: the propyl derivative and COC were then recovered by liquid-liquid extraction procedure. Gas chromatography-mass spectrometry was used to detect the analytes in selected ion monitoring mode. The method proved to be precise for BZE and COC both in term of intraday and interday analysis, with a coefficient of variation (CV) 2>0.999 and >0.997, respectively) within the range investigated. The method, applied to thirty authentic samples, showed to be very simple, fast, and reliable, so it can be easily applied in routine analysis for the quantification of BZE and COC in urine samples

Renaissance mercurial therapy in the mummies of Saint Domenico Maggiore in Naples: a palaeopathological and palaeotoxicological approach

AbstractThis study was designed to evaluate the use of mercury therapy in the Italian noble classes of the Renaissance through the toxicological analysis of hair content. Mercury has stability and a long half-life in hair, representing a great resource not only for forensic toxicological analysis but also for archaeological research on mercurial exposure in past populations. The hair of fourteen mummified individuals of the Aragon and vice-royal court of Naples, buried in the Neapolitan Basilica of Saint Domenico Maggiore (15–18th centuries), was analysed by atomic absorption spectroscopy (AAS) and flame emission spectroscopy (FES). Out of the fourteen individuals, four presented mercury concentrations in the hair washing liquid indicating external perimortem application (in one case clearly linked to embalming, in three cases probably associated with topical therapeutic practices), three showed no traces of mercury, and seven had mercury values in hair ranging from 411 to 47 ppm, which indicate prolonged exposure in life to the metal. The historical identification of most of the mummified bodies with important nobles of Naples has allowed to compare the toxicological analyses with the nosography of the individuals and with the palaeopathological results deriving from the direct study of their bodies. Prolonged exposure in life to the metal was most likely due to mercurial anti-syphilitic therapy, as a consequence of its indiscriminate use in Renaissance therapies and, indirectly, as an effect of the extraordinary spread of venereal syphilis in the Italian upper classes during the "epidemic" phase of the disease

Voltage-operated potassium (Kv) channels contribute to endothelium-dependent vasorelaxation of carvacrol on rat aorta

OBJECTIVES: Carvacrol, a monoterpene widely present in nature, is commonly used in the food industry and in cosmetics, besides to possess a plethora of pharmacological properties, among these also in vitro vasorelaxing effects and in vivo hypotensive responses. Although in rat aortic rings carvacrol evoked a vasodilatation both in the presence and in the absence of endothelium, in preparations with intact endothelial layer its vasoactive response markedly improved. METHODS: This study aimed at investigating the mechanism of action responsible for the endothelial component of the carvacrol-induced vasorelaxing response observed in rat isolated aortic rings. KEY FINDINGS: Pharmacological characterization led us to exclude the involvement of NO pathway (neither L-NAME, NO biosynthesis inhibitor, nor ODQ, guanylate cyclase inhibitor, was able to modify the vascular effects of carvacrol) and of arachidonic acid cascade (no inhibitor intercepting the cascade influenced the endothelial-dependent vasodilatation of the monoterpene). Moreover, endothelial TRP channels were also not involved, as capsazepine did not antagonize vasorelaxing effect. Finally, endothelial potassium channels were considered as possible targets of carvacrol; indeed, two voltage-operated potassium (Kv) channel blockers, 4-aminopyridine and quinine, significantly reduced carvacrol potency and efficacy indices. CONCLUSIONS: Kv channels seem to be responsible for vascular effects of the monoterpene typical of Labiatae family

Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

Aims. To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies. Methods. Thirty-eight patients received 500 mg/mq2 CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 100 mg/twice a day UFT p.o. and 200 mg/twice a day CXB p.o. Tegafur, 5-FU, 5-FUH2, GHB and uracil pharmacokinetics were assessed. Plasma vascular endothelial growth factor (VEGF), soluble VE-cadherin (sVE-C) and thrombospondin-1 (TSP-1) levels were detected by ELISA and real-time PCR of CD133 gene expression on peripheral blood mononuclear cell was also performed. Results Seventeen patients (45%) obtained stable disease (SD) with a median duration of 5.8 ms (range, 4.2–7.4). Median progression free survival (PFS) and overall survival (OS) were 2.7 ms (95% CI, 1.6–3.9 ms) and 7.1 ms (95% CI, 4.3–9.9 ms), respectively. No toxicities of grade >1 were observed. Pharmacokinetics of 27 patients (13/14, SD/progressive disease, PD) after the first treatment of UFT revealed that 5-FU AUC and Cmax values greater than 1.313 h x microg/ml and 0.501 microg/ml, respectively, were statistically correlated with stabilization of disease and prolonged PFS/OS. VEGF and sVE-C plasma levels were greater in the PD group when compared to SD group. CD133 expression increased only in the PD patients. Conclusion. Metronomic UFT and CTX with CXB in heavily pre-treated gastrointestinal patients were well tolerated and associated with interesting activity. Potential predictive pharmacokinetic parameters and pharmacodynamic biomarkers have been found

A METHOD AND A DEVICE FOR ASSESSING WHETHER A DRUG OF ABUSE AND/OR A METABOLITE THEREOF IS PRESENT IN A KERATIN MATERIAL

A method and a device, for assessing whether a drug of abuse and/or a metabolite of a drug of abuse is present in a keratin material, where the method includes extracting a drug of abuse and/or a metabolite from a subject’s keratin material, by prearranging an amount of the keratin material; prearrang ing an extraction composition; bringing the keratin material into contact with the extraction composition in order to obtain an extract that contains the drug of abuse and/or the metabo lite, wherein the extraction composition contains a compound selected among urea and urea derivatives