The inhalational administration of drugs is a practical and non-invasive approach with the potential to reduce side effects and with a quick onset of therapeutic activity.Perillyl alcohol (POH) is a monoterpene with antitumor activity that currently is undergoing clinical evaluation as an inhalational anticancer agent. A detection method was developed that will be applicable to pharmacokinetic studies of not only POH, but also its longer-lived main metabolite, perillic acid (PA), in lung tissue and plasma after inhalational delivery. The anticancer activity of POH was investigated in vitro with the use of various lung cancer cell lines. Toxicity was established by a standard MTT assay, and apoptosis markers were analyzed by Western blot. For the detection of POH and PA in lungs and plasma, albino Wistar rats were used that were exposed to POH inhalation. Tissues were subjected to chromatographic separation on an Agilent Zorbax Eclipse XDB C 18 column, followed by detection of absorption in the ultraviolet (UV) range. In vitro, POH exerted cytotoxic activity against six different lung tumor cell lines, and apoptotic cell death was indicated by induction of active caspase 3 and cleavage of poly (ADP-ribose) polymerase 1 (PARP1). These results demonstrate that inhalational delivery of POH results in effective biodistribution and metabolism of POH in the systemic circulation. In addition, our study introduces a simple, rapid HPLC-UV method with high accuracy for simultaneous detection of POH and its metabolite PA in plasma, and for sensitive detection of PA in lung tissue, which should prove useful for applications in clinical studies. K E Y W O R D SHPLC, inhalation, perillic acid, perillyl alcohol, Ras oncoprotein
Em 1969, Michel Foucault (1926-1984) se tornou chefe do departamento de filosofia da Universidade de Vincennes e publicou Archéologie du Savoir. Um ano intenso, no qual Foucault passa a encarnar a figura de intelectual engajado, o que se relaciona tanto com a experiência efervescente em Vincennes como primeiro período de sua obra, a Arqueologia (década de 1960). Ou seja, diferentemente das interpretações clássicas que atribuem apenas ao seu segundo período, a Genealogia (década de 1970), uma dimensão política, havia na Arqueologia um potencial para suscitar novas formas de engajamento político
Question: Mercury is thought to be deposit in amalgam tattoo, which are oral localized black-bluish pigmentation, but there are no reports documenting the presence of inorganic and/or organic mercury in amalgam tattoos in the oral cavity in humans.Methods: The content of total mercury in amalgam tattoo due to mercury released from mercury-containing amalgam fillings was determined in 5 specimens of amalgam tattoo. We analyzed at about 50-200 mg wet weight of tissue for each specimen and fixed in 10 percent formaldehyde, and compared with the levels of total mercury of 20 gingiva specimens without amalgam tattoo.Results: Total mercury levels were elevated in all specimens of amalgam tattoo we analyzed (5 of 5), as it greatly exceeds the normal range 2 g/g (toxic level, >200). The mean mercury level in amalgam tattoo was 82.12 g/g as compared with 0.204 micrograms per gram in controls. We found that the content of the total mercury in amalgam tattoo specimens ranged from 3.2 to 358 g/g. In one amalgam tattoo tissue with the highest mercury level was also observed a high level of silver (Ag) 94.5 g/g (threshold limit value).Conclusions: Amalgam tattoo had elevated total mercury levels. Hair analysis provides information about use of drugs over a long period. In the present study a methodology aimed the simultaneous quantification of buprenorphine, of methadone and its metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrrolidine (EMDP), and of heroin metabolites, morphine and 6-acetylmorphine (6-AM), in hair samples collected from drug abusers enrolled in methadone treatment program for heroine addition. Ethylmorphine was used as internal standard. Washing, spiking and extraction studies of hair drugs were developed. After decontamination with n-hexane, an amount of 30 mg of powdered real hair samples were placed in a tube and 1 mL of hydrochloric acid 0.1 mol/L. After overnight incubation at 60 • C the solution was neutralized with 1 mL of NaOH 0.1 mol/L and buffered with 1 mL of phosphate buffer pH 7.0. Samples were centrifuged at 4000 rpm for 5 min, the supernatant being collected and purified by solid-phase extraction using mixed-mode extraction cartridges (MCX). The analytes were eluted with 2 mL of a mixture of methanol:ammonia (5%). The obtained solutions were evaporated to dryness under a stream of nitrogen and subsequently resuspended with 50 L derivatizing N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA). Blank, standards and samples were analyzed by gas chromatography/electron impact-mass spectrometry (GC-EI/MS). Selectivity, linearity, analytical limits (i.e., limit of detection and low limit of quantification -LOD and LLOQ), carryover, precision, accuracy and recovery were evaluated. A number of 10 hair samples from human subjects following a long-term methadone therapy were analyzed by this method. All analytes were identified except EMDP, possibly because its represents less than 10% of methadone metabolites and hair excretion may not be s...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.