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  • articleFree Access

    ENHANCED FLUORESCENCE IMAGING WITH DMSO-MEDIATED OPTICAL CLEARING

    Recent studies have demonstrated that topical application of glycerol on intact skin does not affect its optical scattering properties. Investigators from our research group recently revisited the use of dimethyl sulfoxide (DMSO) as an agent with optical clearing potential. We address the use of optical clearing to enhance quantitation of subsurface fluorescence emission. We employed both in vitro and in vivo model systems to study the effect of topical DMSO application on fluorescence emission. Our in vitro experiments performed on a tissue-simulating phantom suggest that DMSO-mediated optical clearing enables enhanced characterization of subsurface fluorophores. With topical DMSO application, a marked increase in fluorescence emission was observed. After 30 min, the fluorescence signal at the DMSO-treated site was 9× greater than the contralateral saline-treated site. This ratio increased to 13× at 105 min after agent application. In summary, DMSO is an effective optical clearing agent for improved fluorescence emission quantitation and warrants further study in preclinical in vivo studies. Based on outcomes from previous clinical studies on the toxicity profile of DMSO, we postulate that clinical application of DMSO as an optical clearing agent, can be performed safely, although further study is warranted.

  • articleOpen Access

    Upconversion nanoparticle as a theranostic agent for tumor imaging and therapy

    Upconversion nanoparticles (UCNPs) as a promising material are widely studied due to their unique optical properties. The material can be excited by long wavelength light and emit visible wavelength light through multiphoton absorption. This property makes the particles highly attractive candidates for bioimaging and therapy application. This review aims at summarizing the synthesis and modification of UCNPs, especially the applications of UCNPs as a theranostic agent for tumor imaging and therapy. The biocompatibility and toxicity of UCNPs are also further discussed. Finally, we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for tumor imaging and therapy.

  • chapterFree Access

    TOXICITY VERSUS POTENCY: ELUCIDATION OF TOXICITY PROPERTIES DISCRIMINATING BETWEEN TOXINS, DRUGS, AND NATURAL COMPOUNDS

    Within our everyday life we are confronted with a variety of toxic substances. A number of these compounds are already used as lead structures for the development of new drugs, but the amount of toxic substances is still a rich resource of new bioactive compounds. During the identification and development of new potential drugs, risk estimation of health hazards is an essential and topical subject in pharmaceutical industry. To face this challenge, an extensive investigation of known toxic compounds is going to be helpful to estimate the toxicity of potential drugs. "Toxicity properties" found during those investigations will also function as a guideline for the toxicological classification of other unknown substances. We have compiled a dataset of approximately 50,000 toxic compounds from literature and web sources. All compounds were classified according to their toxicity. During this study the collection of toxic compounds was investigated extensively regarding their chemical, functional, and structural properties and compaired with a dataset of drugs and natural compounds. We were able to identify differences in properties within the toxic compounds as well as in comparison to drugs and natural compounds. These properties include molecular weight, hydrogen bond donors and acceptors, and functional groups which can be regarded as "toxicity properties", i.e. attributes defining toxicity.

  • chapterFree Access

    Chapter 1.1: Drug Metabolism and Pharmacogenetics Then and Now

    Arylamine N-acetyltransferases (NAT, EC 2.3.1.5) were amongst the first enzymes known to result in a genetically determined response to a drug, in this case isoniazid. We now know there are two functional NAT genes in humans and these encode (HUMAN)NAT1 and (HUMAN)NAT2 enzymes. The NAT genes are each encoded at polymorphic loci. This chapter explores the early studies on phenotypic variation in NAT activity and discusses how genotyping of (HUMAN)NAT1 and (HUMAN)NAT2 has changed since NAT pharmacogenetics were first described 50 years ago. The relationship between clinical and molecular studies on genes and proteins has provided current understanding of the NAT enzymes and their genes in humans, where evidence indicates (HUMAN)NAT1 has an endogenous role in addition to a drug metabolising role. NATs in other animal species, bacteria and fungi, are also introduced and polymorphisms in other species are described. Enzymic and later structural studies established that the acetylation reaction involved the transfer of an acetyl group to a cysteine sulphydryl group, activated as part of a juxtaposed catalytic traid with aspartate and histidine in all NAT enzymes with only one exception in bacteria to date. The body of research on NATs has laid the foundation for an exciting period to come encompassing whole genome analyses and understanding epigenetic control to allow exploitation of NAT biology in order to understand and perhaps treat disease.