The role of alternative specimens in toxicological analysis

The use of alternative specimens in the field of toxicology was first described in 1979, where hair analysis was used to document chronic drug exposure. Since then, the use of these “alternative” samples has gained tremendous importance in forensic toxicology, as well as in clinic toxicology, doping control and workplace drug testing. It’s not surprising, therefore, that a big number of papers dealing with the determination of several classes of drugs in saliva, sweat, meconium and hair have been published ever since, which is due to the fact that chromatographic equipments are becoming more and more sensitive being mass spectrometry (and tandem mass spectrometry) the most widely used analytical tool, combined with gas or liquid chromatography. “Alternative” specimens present a number of advantages over the “traditional” samples normally used in toxicology (e.g. blood, urine and tissues), namely the fact that their collection is not invasive, their adulteration is difficult, and they may allow the increasing of the windows of detection for certain drugs. The main disadvantage of this kind of samples is that drugs are present in very low concentrations, and therefore high sensitive techniques are required to accomplish the analysis. This paper reviews a series of publications on the use of alternative specimens, with special focus on the main analytical and chromatographic problems that these samples present, as well on their advantages and disadvantages over traditional samples in documenting drug exposure

Secondary Metabolites and Their Applications

The identification of secondary metabolites present in both terrestrial and marine species continues to be a fundamental and privileged path for the emergence of new and fundamental natural products available on the market with very different applications. For example, aplidine is a new natural anticancer agent, and it was approved in Australia in 2018 to treat multiple myeloma and was isolated from the first time from tunicate “Aplidium albicans” Milne Edwards. (+)-Nootkatone is a natural sesquiterpene compound, found in very small amounts in several species such as “Chamaecyparis nootkatensis” (D. Don) Sudworth, ”Chrysopogon zizanioides” (L.) Roberty and “Citrus paradise” Macfad., which exhibits highly appreciated organoleptic properties and is, therefore, highly demanded as a flavoring agent or adjuvant in the food, pharmaceutical and perfumery industries. This same natural secondary metabolite is applied as insecticide and acaricide, and it was very recently authorized by United Sates Environmental Protection Agency to be include on formulations to control the spread of mosquitoes that transmit infectious diseases as dengue and zika. And who does not know the application of ascorbic acid, found for example in acerola and lemon fruits, as an antioxidant agent, widely used by the food industry? The successful application of secondary metabolites in diverse requests often involves the use of, more or less, complex mixtures of metabolites, extracted by different methods and from different natural sources, but whose chemical composition and active principles are perfectly established. For example, there are the defined botanical mixtures, called natural product botanicals, which are recognized by the FDA as medicinal entities, successfully used in clinical therapy for the treatment of various diseases. This is the case of the mixture of the secondary metabolites of ”Solanum sodomaeum” L., solamargine, solasonine, and mono- and di-glycosides derivatives of solasodine, approved by the European Medicine Agency (trade name Curaderm) for the treatment of basal cell carcinoma of the skin. One area in which the application of secondary metabolites mixtures rather than of pure compounds is common is in the formulation of biopesticides. For example, the insecticide Grandevo® is a mixture of metabolites produced in the fermentation of “Chromobacterium subtsugae”, which includes pigments from the violacein family and proteins that are repellent and antifeeding. Despite the great successes already achieved regarding the secondary metabolites’ identification and the development of new applications for these metabolites, this is an area of research that should not slow down. Research must continue identifying and isolating secondary metabolites in unexplored natural sources; new methodologies for extracting secondary metabolites should be tested and optimized to develop greener and more efficient processes; pure secondary metabolites and chemically characterized mixtures must be tested in different biological activities in order to enhance new applications responding to the growing needs of humanity. The Special Issue of Applied Sciences, “Advances in Applications of Natural Bioactive Compounds”, aims to contribute to the desired continuous advance in this scientific field, bringing together publications focused on the most recent advances in the identification of secondary metabolites from terrestrial and marine sources, in new extractive methodologies, and in proposals for applications that add value to natural resources and contributes to a more sustainable development.his study was financed by Portuguese National Funds, through FCT Fundação para a Ciência e Tecnologia, the European Union, QREN, FEDER, and COMPETE, through funding the cE3c center (UIDB/00329/2020), the LAQV-REQUIMTE (UIDB/50006/2020) and the CICS-UBI (UIDB/00709/2020 and UIDP/00709/2020).info:eu-repo/semantics/publishedVersio

A review of current bioanalytical approaches in sample pretreatment techniques for the determination of antidepressants in biological specimens

Antidepressants are a class of compounds widely used in clinical settings for the treatment of several diseases. In the last years there has been a considerable increase in their consumption, representing an important public health issue in several countries. Because they are substances with narrow therapeutic windows, and since they are capable of interacting with other classes of compounds, monitoring of these compounds is of relevance, minimizing the risk of medical interactions as well as side and toxic effects. In addition, understanding the extent of their use, their detection through routine toxicology tests and development of new methods for detection and monitoring is of extreme importance concerning public health, patient well-being, and implications in clinical and forensic situations. The main objective of this work is to perform a critical review on the biological samples used in the detection and quantification of antidepressants with special focus on the techniques for sample preparation.info:eu-repo/semantics/publishedVersio

Current Technologies and Considerations for Drug Bioanalysis in Oral Fluid

Oral fluid analysis for drugs was first used almost 30 years ago for the purpose of therapeutic drug monitoring. Since then, oral fluid bioanalysis has become more popular, mainly in the fields of pharmacokinetics, workplace drug testing, criminal justice, driving under the influence testing programs, and therapeutic drug monitoring. In fact, oral fluid can provide a readily available and non-invasive medium, without any privacy loss by the examinee, which occurs for instance during the collection of urine samples. It is believed that drug concentrations in oral fluid may parallel those measured in blood. This feature makes oral fluid an alternative analytical specimen to blood, which assumes particular importance in roadside testing, the most published application of this sample. Great improvements in the development of accurate and reliable methods for sample collection, in situ detection devices (on-site drug detection kits), and highly sensitive and specific analytical methods for oral fluid testing of drugs have been observed in the last years. However, without mass spectrometry-based analytical methods, e.g. liquid chromatography coupled to mass spectrometry (LC/MS) or tandem mass spectrometry (LC/MS/MS), the desired sensitivity would not be met, due to the low amounts of sample usually available for analysis. This review will discuss a series of published papers on the applicability of oral fluid in the field of analytical, clinical and forensic toxicology, with special focus on its advantages and drawbacks over the normally used biological specimens and the main technological advances over the last decade, which made possible oral fluid bioanalysis for drugs

Advances on Applications of Bioactive Natural Compounds

This is a reprint of articles from the Special Issue published online in the open access journal Applied Sciences (ISSN 2076-3417) (available at: https://www.mdpi.com/journal/applsci/special issues/Bioactive Natural Compounds).info:eu-repo/semantics/publishedVersio

Analysis of Cannabinoids in Biological Specimens: An Update

Cannabinoids are still the most consumed drugs of abuse worldwide. Despite being considered less harmful to human health, particularly if compared with opiates or cocaine, cannabis consumption has important medico-legal and public health consequences. For this reason, the development and optimization of sensitive analytical methods that allow the determination of these compounds in different biological specimens is important, involving relevant efforts from laboratories. This paper will discuss cannabis consumption; toxicokinetics, the most detected compounds in biological samples; and characteristics of the latter. In addition, a comprehensive review of extraction methods and analytical tools available for cannabinoid detection in selected biological specimens will be reviewed. Important issues such as pitfalls and cut-off values will be considered.info:eu-repo/semantics/publishedVersio

Natural Products: Therapeutic Properties and Beyond II

Historically, natural products have contributed to drug discovery as a source of active molecules due to their great diversity and structural complexity. Thus, they have contributed to the development of drugs for applications in different therapeutic areas. In recent decades, there has been a paradigm shift in drug discovery strategies that has allowed for identifying new natural products that exhibit activities on therapeutic targets. Newman and Cragg studied the origin of 1330 new drugs that had been approved between 1981 and 2010 and found that 64% of them were somewhat related to natural compounds [1]. In a recent review by these same authors, it was noted that, within all of the drugs newly approved by the Food and Drug Administration between January 1981 and September 2019, compounds derived from natural products ranked second [2]. Besides the importance of the discovery of new molecules based on natural compounds, the concern today is focused on the therapeutic potential of secondary metabolites classified as drugs of abuse, such as derivatives of cannabis [3] and psilocybin [4], or even on the use of plants used ancestrally in medicine as well [5,6]. On the other hand, with the development of computational techniques, a decision has been made to study the possibilities of analyzing the pharmacological potential of natural products or their derivatives and converting these molecules into low toxicity active products. However, apart from the use of naturally occurring compounds in the field of health, they have been studied and are increasingly used in solutions, for instance in the agrochemical and food industries. After the success of the Special Issue “Natural Products: Therapeutic Properties and Beyond I”, this second edition aims to categorize the state of the art concerning scientific research on natural products, including their applications as compounds with added value to human health. This issue intends to be used as a text for academia or as a reference tool for researchers, particularly for those working in the fields of medicinal chemistry, toxicology, phytochemistry, and natural product chemistry, and for health and industry professionals.info:eu-repo/semantics/publishedVersio

Natural Products: Therapeutic Properties and Beyond II

Historically, natural products have contributed to drug discovery as a source of active molecules due to their great diversity and structural complexity. Thus, they have contributed to the development of drugs for applications in different therapeutic areas. In recent decades, there has been a paradigm shift in drug discovery strategies that has allowed for identifying new natural products that exhibit activities on therapeutic targets. Newman and Cragg studied the origin of 1330 new drugs that had been approved between 1981 and 2010 and found that 64% of them were somewhat related to natural compounds [1]. In a recent review by these same authors, it was noted that, within all of the drugs newly approved by the Food and Drug Administration between January 1981 and September 2019, compounds derived from natural products ranked second [2]. Besides the importance of the discovery of new molecules based on natural compounds, the concern today is focused on the therapeutic potential of secondary metabolites classified as drugs of abuse, such as derivatives of cannabis [3] and psilocybin [4], or even on the use of plants used ancestrally in medicine as well [5,6]. On the other hand, with the development of computational techniques, a decision has been made to study the possibilities of analyzing the pharmacological potential of natural products or their derivatives and converting these molecules into low toxicity active products. However, apart from the use of naturally occurring compounds in the field of health, they have been studied and are increasingly used in solutions, for instance in the agrochemical and food industries. After the success of the Special Issue “Natural Products: Therapeutic Properties and Beyond I”, this second edition aims to categorize the state of the art concerning scientific research on natural products, including their applications as compounds with added value to human health. This issue intends to be used as a text for academia or as a reference tool for researchers, particularly for those working in the fields of medicinal chemistry, toxicology, phytochemistry, and natural product chemistry, and for health and industry professionals.info:eu-repo/semantics/publishedVersio

Higher Education Systems and Institutions, Costa Rica

Costa Rica was a marginal and sparsely populated province of the Spanish Empire during the colonial period (1580–1821). Those interested in pursuing higher education were therefore forced to travel abroad, especially to Nicaragua or Guatemala, where those who chose to pursue nonclerical studies could degree in Medicine and Law, which facilitated the development of an intelligentsia with liberal ideas (González 2006). The Casa de Enseñanza de Santo Tomás was founded in 1814, at the initiative and with the funding of the residents of the City of San José. This institution of religious orientation, focused on primary and secondary levels, would 29 years later become the Universidad de Santo Tomás, the first higher education institution in the country (Molina 2016).UCR::Vicerrectoría de Docencia::Centro de Evaluación Académic

Implementación de la acreditación de carreras como un componente de la política de aseguramiento de la calidad: análisis a partir de los discursos de los actores y los mecanismos adoptados en el ámbito de la educación superior pública costarricense 1999-2016

En la presente investigación se planteó como problema de estudio examinar el proceso de implementación de la acreditación de carreras como un componente de la política de aseguramiento de la calidad, a partir tanto de las interacciones de los diversos actores y sus discursos, como de los mecanismos adoptados en el ámbito de la educación superior pública costarricense. El análisis se concentró en las etapas de formulación e implementación, realizándose para el SINAES en general y para el caso de las carreras de educación de la UNA y de la UCR, durante el periodo 1999-2016. El objeto de estudio se abordó desde el enfoque del institucionalismo centrado en actores, el cual parte de la idea de la conformación de redes de actores públicos y privados en las actividades del sector público, circunscritas en un marco institucional que influye tanto sobre actores como en los resultados políticos (Zurbringgen, 2006). Adicionalmente se utilizaron los marcos analíticos de política pública de Mazmanian y Sabatier (1981) y el modelo de Scharfp (1997). Para cumplir los objetivos de investigación se realizó una revisión documental de leyes, normativa y actas. Se identificaron las interacciones de actores en las actas del Consejo Nacional de Acreditación (CNA) y en los medios de comunicación utilizando la técnica análisis de redes (ARS). También se utilizó el análisis crítico del discurso (ACD) para establecer los discursos de autoridades universitarias, autoridades de gobierno y medios de comunicación. Finalmente, se realizaron entrevistas semiestructuradas dirigidas a docentes y directoras de las carreras de educación de la UNA y UCR para identificar la noción de calidad, motivaciones y apoyo hacia la acreditación. Los análisis mostraron que en la etapa de formulación de la política de aseguramiento de la calidad se tendió a vincular con la idea de educación como derecho humano, mientras que, en el periodo de implementación se enfatiza el condicionamiento de las ayudas económicas al mejoramiento y desarrollo de indicadores relacionados con el control y la rendición de cuentas por parte de las universidades. Por otra parte, el análisis de la noción de calidad mostró que no existe una única definición. Para el caso del SINAES esta está condicionada a la misión y metas que se propone cada universidad, mientras que la UNA y UCR se apartan de esta noción relativista e indican que se debe responder al contexto -agenda educativa del país- y formar buenos profesionales. Además, los discursos utilizados funcionaron como una herramienta persuasiva, ya que, al no estar el concepto de calidad universitaria claro para los diversos actores, se logra posicionar la relevancia de la acreditación de carreras vinculándola con la excelencia, la rendición de cuentas, la mejora continua y como una herramienta para responder a la sociedad del conocimiento. Tanto el SINAES como las universidades públicas analizadas han establecido un marco institucional y una gobernanza para implementar la acreditación. En cuanto al nivel de apoyo público a la acreditación de carreras se encontró que la acreditación es importante, ya que podría brindar información tanto a padres de familia como estudiantes sobre la calidad de las universidades y sus carreras con vistas a la consolidación de una cultura de rendición de cuentas. Finalmente, en cuanto al análisis de las interacciones de los actores, se puede definir como una política de alto consenso, se encuentra un único disenso marcado por dos constelaciones de actores una a favor del SINAES y otra que consideraba que debía existir un ente acreditador únicamente para universidades privadas; sin embargo, ambas constelaciones poseen una posición a favor de la acreditación. Conforme se avanza en la acreditación se resalta que esta presenta una baja cobertura y se relaciona como un elemento a mejorar por parte del SINAES.UCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Ciencias Sociales::Doctorado Académico en Gobierno y Políticas Pública