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1.
PLoS One ; 17(4): e0266419, 2022.
Article in English | MEDLINE | ID: mdl-35385518

ABSTRACT

The pandemic caused by the SARS-CoV-2 virus (COVID-19) is still a major health issue. The COVID-19 pandemic has forced the university teaching to consider in high priority the switch from in-presence teaching to remote teaching, including laboratory teaching. While excellent virtual-laboratory teaching has been proposed and turned out to be very useful, the need of a real-laboratory in-presence teaching is still a major need. This study was aimed at presenting a laboratory exercise focusing (a) on a very challenging therapeutic strategy, i.e. SARS-CoV-2 diagnostics, and (b) on technologies that are playing a central role in applied biochemistry and molecular biology, i.e. PCR and RT-PCR. The aims of the practical laboratory were to determine: (a) the possibility to identify SARS-CoV-2 sequences starting from a recombinant plasmid and (b) the possibility to discriminate cells with respect to the expression of SARS-CoV-2 Spike protein. This activity is simple (cell culture, RNA extraction, RT-qPCR are all well-established technologies), fast (starting from isolated and characterized RNA, few hours are just necessary), highly reproducible (therefore easily employed by even untrained students). We suggest that this laboratory practical exercises should be considered for face-to-face teaching especially if the emergency related to the COVID-19 pandemic is maintained. The teaching protocol here described might be considered in order to perform fast but meaningful in-presence teaching, making feasible the division of crowded classes in low-number cohorts of students, allowing the maintenance of the required social distance.


Subject(s)
Biochemistry , Pharmacology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Teaching , Biochemistry/education , Pharmacology/education , RNA , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
2.
Methods Mol Biol ; 2486: 71-86, 2022.
Article in English | MEDLINE | ID: mdl-35437719

ABSTRACT

Significant advances in analytical technologies have dramatically improved our ability to deconvolute disease biology at molecular, cellular, and tissue levels. Quantitative system pharmacology (QSP) modeling is a computational framework to systematically integrate pharmaceutical properties of a drug candidate with scientific understanding of that deeper disease etiology, target expression, genetic variability, and human physiological processes, thus enabling more insightful drug development decisions related to efficacy and safety. In this chapter, we discuss the key attributes of QSP models in comparison to traditional models. We discuss a recommended four-step process to construct a QSP model to support drug development decisions. A number of illustrative QSP examples related to high-value drug development questions and decisions impacting target identification, lead generation and optimization, first in human studies, and clinical dose and schedule optimization are covered in the chapter. The future perspectives of QSP in the context of potential regulatory acceptance are also discussed.


Subject(s)
Models, Biological , Pharmacology , Drug Development , Humans
3.
Methods Mol Biol ; 2486: 129-179, 2022.
Article in English | MEDLINE | ID: mdl-35437722

ABSTRACT

Quantitative systems pharmacology (QSP) places an emphasis on dynamic systems modeling, incorporating considerations from systems biology modeling and pharmacodynamics. The goal of QSP is often to quantitatively predict the effects of clinical therapeutics, their combinations, and their doses on clinical biomarkers and endpoints. In order to achieve this goal, strategies for incorporating clinical data into model calibration are critical. Virtual population (VPop) approaches facilitate model calibration while faced with challenges encountered in QSP model application, including modeling a breadth of clinical therapies, biomarkers, endpoints, utilizing data of varying structure and source, capturing observed clinical variability, and simulating with models that may require more substantial computational time and resources than often found in pharmacometrics applications. VPops are frequently developed in a process that may involve parameterization of isolated pathway models, integration into a larger QSP model, incorporation of clinical data, calibration, and quantitative validation that the model with the accompanying, calibrated VPop is suitable to address the intended question or help with the intended decision. Here, we introduce previous strategies for developing VPops in the context of a variety of therapeutic and safety areas: metabolic disorders, drug-induced liver injury, autoimmune diseases, and cancer. We introduce methodological considerations, prior work for sensitivity analysis and VPop algorithm design, and potential areas for future advancement. Finally, we give a more detailed application example of a VPop calibration algorithm that illustrates recent progress and many of the methodological considerations. In conclusion, although methodologies have varied, VPop strategies have been successfully applied to give valid clinical insights and predictions with the assistance of carefully defined and designed calibration and validation strategies. While a uniform VPop approach for all potential QSP applications may be challenging given the heterogeneity in use considerations, we anticipate continued innovation will help to drive VPop application for more challenging cases of greater scale while developing new rigorous methodologies and metrics.


Subject(s)
Pharmacology , Algorithms , Calibration , Models, Biological , Systems Biology/methods
4.
Methods Mol Biol ; 2486: 335-343, 2022.
Article in English | MEDLINE | ID: mdl-35437730

ABSTRACT

There is a demand for scientists trained in quantitative systems pharmacology (QSP) that has yet to be met by changes in graduate education. The multidisciplinary nature of QSP is not unlike its predecessor, pharmacokinetics (PKs) and pharmacodynamics (PDs) that have now become firmly established in many educational programs. A hindrance to the evolution of educational programs for QSP is explored and suggestions to move QSP into its proper position as a unique discipline are presented.


Subject(s)
Pharmacology , Models, Biological
5.
Nihon Yakurigaku Zasshi ; 157(2): 100-103, 2022.
Article in Japanese | MEDLINE | ID: mdl-35228438

ABSTRACT

Among medical care incidents in Japan, an increase in medicine-related errors by nurses have been reported. These errors may be caused by a lack of knowledge of clinical pharmacology and drug interactions. It is important for nurses to acquire risk-management skills based on clinical pharmacology. In order to improve fundamental knowledge in pharmacology and clinical pharmacology for nurses, various training programs exist. We reviewed a number of educational programs in medicine and report our results. Based on our results, it is necessary for medical education programs to include the following 5 essential elements: 1) An analysis of frequently-occurring medication errors in the field of clinical pharmacology, 2) drugs administer for patient characteristic and patient observation practices, 3) an emphasis on the interactions between drugs and food or other drugs, 4) assessment of patient symptoms, risk-management, and the efficacy of drugs, 5) the necessity of using the package inserts. In a new curriculum, it is necessary to have systematic, step by step training in pharmacology and clinical pharmacology. It is also necessary to develop these teaching methods in cooperation with specialists and experts in the field.


Subject(s)
Education, Nursing , Pharmacology, Clinical , Pharmacology , Curriculum , Humans , Japan , Pharmacology/education , Pharmacology, Clinical/education
7.
J Med Chem ; 65(4): 3606-3615, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35138850

ABSTRACT

The origin of small-molecule leads that were pursued across the independent research organizations Roche and Genentech from 2009 to 2020 is described. The identified chemical series are derived from a variety of lead-finding methods, which include public information, high-throughput screening (both full file and focused), fragment-based design, DNA-encoded library technology, use of legacy internal data, in-licensing, and de novo design (often structure-based). The translation of the lead series into in vivo tool compounds and development candidates is discussed as are the associated biological target classes and corresponding therapeutic areas. These analyses identify important trends regarding the various lead-finding approaches, which will likely impact their future application in the Roche and Genentech research groups. They also highlight commonalities and differences across the two independent research organizations. Several caveats associated with the employed data collection and analysis methodologies are included to enhance the interpretation of the presented information.


Subject(s)
Drug Discovery/trends , Drug Industry/trends , Pharmacology/trends , Small Molecule Libraries , DNA/chemistry , DNA/genetics , High-Throughput Screening Assays , Humans , Research Design
8.
Pharmacol Res Perspect ; 10(1): e00908, 2022 02.
Article in English | MEDLINE | ID: mdl-35147294

ABSTRACT

Regarding animal experiments in pharmacology teaching, ethical considerations led us to examine an alternative approach to the use of living animals. This study aimed to assess whether digital tools could replace live animal experiments in terms of motivation and knowledge acquisition. The study was carried out with students enrolled in the 5th year of the industry/research stream at the Faculty of Pharmacy of the University of Limoges. The participants were randomly assigned to groups of traditional or digital teaching methods, with the common theme of the class being the effect of a diuretic agent (furosemide) in rats. The scenario and learning objectives were identical for the two groups. Before the class and after randomization, the acceptance of the digital educational material was assessed with a scale, which predicts the acceptability of users according to individual dimensions and social representations, followed by the assessment of the motivation by a situational motivation scale (SIMS) for both groups. After the class, the students' motivation was assessed by a questionnaire based on Deci and Ryan's self-determination theory. In the end, the participants were evaluated for homogeneity, based on general knowledge of renal pharmacology, and for knowledge acquisition concerning specific knowledge related to this teaching session. This study revealed a good acceptance of the digital tool and a good motivation toward the digital method among all the students. It found the two teaching methods (digital and traditional) to be equivalent in terms of motivation and knowledge acquisition. In our study, digital pedagogical tools as an alternative to live animals did not affect students' motivation and knowledge acquisition.


Subject(s)
Animal Testing Alternatives/methods , Education, Pharmacy/methods , Pharmacology/education , Students, Pharmacy/psychology , Animals , Computer-Assisted Instruction/methods , Diuretics/pharmacology , Educational Measurement , Educational Technology/methods , France , Furosemide/pharmacology , Humans , Motivation , Rats , Surveys and Questionnaires
9.
Adv Drug Deliv Rev ; 182: 114116, 2022 03.
Article in English | MEDLINE | ID: mdl-35085623

ABSTRACT

Due to the increasing population of individuals with cardiovascular diseases and related comorbidities, there is an increasing need for development of synergistic therapeutics. Monocytes are implicated in a broad spectrum of diseases and can serve as a focal point for therapeutic targeting. This review discusses the role of monocytes in cardiovascular diseases and highlights trends in monocyte targets nanoparticles in three cardiovascular-related diseases: Diabetes, Atherosclerosis, and HIV. Finally, the review offers perspectives on how to develop nanoparticle monocyte targeting strategies that can be beneficial for treating co-morbidities.


Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/physiopathology , Macrophages/metabolism , Monocytes/metabolism , /chemistry , Atherosclerosis/drug therapy , Atherosclerosis/epidemiology , Atherosclerosis/physiopathology , Cardiovascular Diseases/epidemiology , Comorbidity , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Diabetes Mellitus/physiopathology , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/physiopathology , Humans , Pharmacokinetics , Pharmacology
11.
Eur J Clin Pharmacol ; 78(4): 691-694, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35037981

ABSTRACT

The European Association for Clinical Pharmacology and Therapeutics (EACPT) is a leading society in Europe serving the European and global Clinical Pharmacology and Therapeutics community. Its specific aims include promotion of the utilisation and divulgation of the utility of clinical pharmacology services in health care delivery. EACPT currently has four active working groups (WGs): Education, Regulatory affairs, Clinical research and Young Clinical Pharmacologists (YCP WG). EACPT YCP WG was established in 2015 with the idea of improving education, research, training and networking/mobility opportunities for YCPs across Europe and globe. The main objective of the present manuscript is to provide detailed information on general characteristics, structure, chronogram, objectives, accomplishments and current/future focus areas of the EACPT YCP WG. Consequently, we tend to notably enhance EACPT YCP WG's visibility, increase the number of its members and mobility/networking options and to expand areas of activity even more. Moreover, by this we can also make clinical pharmacology more attractive to early career fellows and colleagues and empower its position alongside other medical specialties.


Subject(s)
Pharmacology, Clinical , Pharmacology , Delivery of Health Care , Europe , Humans , Pharmacology, Clinical/education
12.
Arch Toxicol ; 96(3): 691-710, 2022 03.
Article in English | MEDLINE | ID: mdl-35006284

ABSTRACT

The pharmacology and toxicology of a broad variety of therapies and chemicals have significantly improved with the aid of the increasing in vitro models of complex human tissues. Offering versatile and precise control over the cell population, extracellular matrix (ECM) deposition, dynamic microenvironment, and sophisticated microarchitecture, which is desired for the in vitro modeling of complex tissues, 3D bio-printing is a rapidly growing technology to be employed in the field. In this review, we will discuss the recent advancement of printing techniques and bio-ink sources, which have been spurred on by the increasing demand for modeling tactics and have facilitated the development of the refined tissue models as well as the modeling strategies, followed by a state-of-the-art update on the specialized work on cancer, heart, muscle and liver. In the end, the toxicological modeling strategies, substantial challenges, and future perspectives for 3D printed tissue models were explored.


Subject(s)
Bioprinting/methods , Models, Biological , Printing, Three-Dimensional , Animals , Extracellular Matrix/metabolism , Humans , Pharmacology/methods , Tissue Engineering/methods , Toxicology/methods
13.
Trends Pharmacol Sci ; 43(2): 136-150, 2022 02.
Article in English | MEDLINE | ID: mdl-34895945

ABSTRACT

For complex diseases, most drugs are highly ineffective, and the success rate of drug discovery is in constant decline. While low quality, reproducibility issues, and translational irrelevance of most basic and preclinical research have contributed to this, the current organ-centricity of medicine and the 'one disease-one target-one drug' dogma obstruct innovation in the most profound manner. Systems and network medicine and their therapeutic arm, network pharmacology, revolutionize how we define, diagnose, treat, and, ideally, cure diseases. Descriptive disease phenotypes are replaced by endotypes defined by causal, multitarget signaling modules that also explain respective comorbidities. Precise and effective therapeutic intervention is achieved by synergistic multicompound network pharmacology and drug repurposing, obviating the need for drug discovery and speeding up clinical translation.


Subject(s)
Pharmacology , Drug Discovery , Humans , Reproducibility of Results
15.
16.
Rev Fac Odont (Córobda) ; 31(3): 29-34, dic. 2021. graf
Article in Spanish | BINACIS, BINACIS, UNISALUD | ID: biblio-1359688

ABSTRACT

ntroducción: La enseñanza de la Farmacología tradicionalmente se ha caracterizado por la transmisión de información donde las estrategias pedagógicas se han centrado en el profesor, privilegiando el conocimiento teórico, las clases magistrales y los exámenes memorísticos. Es imprescindible la introducción de elementos nuevos para aumentar la participación activa del estudiante en la construcción del conocimiento y en la evaluación del logro de sus competencias; el desarrollo de la creatividad y el trabajo en equipo. Esta metodología busca romper la noción de enseñanza tradicional, cambiar la idea de una evaluación por la nota a una evaluación con una motivación propia (del estudiante), para internalizar el conocimiento y hacerlo parte desu estructura de pensamiento. Objetivo: Desarrollar una estrategia de enseñanza y evaluación que permita a los estudiantes participar activamente. Materiales y métodos: Participaron 172 estudiantes que cursaron la asignatura de Farmacología y Terapéutica "B", entre marzo y septiembre de 2017. Se desarrollaron cuatro actividades individuales y complementarias relacionadas con la prescripción de medicamentos, para la evaluación del proceso y desempeño de los estudiantes se emplearon rúbricas normalizadas de evaluación, se aplicó una encuestade percepción a los estudiantes sobre la utilidad de la estrategia en su formación. Resultados: Los resultados muestran un buen desempeño de los estudiantes en las actividades de prescripción de medicamentos, un mejoramiento significativo en el desempeño al comparar los resultados. Los estudiantes consideran que la estrategia es útil para el desarrollo de sus competencias profesionales, les permite tener un papel activo en el proceso de aprendizaje y la metodología de evaluación les permite reconocer los elementos que deben reforzar para llegar a un óptimo desarrollo de su competencia


Subject(s)
Humans , Male , Female , Adolescent , Adult , Pharmacology , Educational Measurement , Interdisciplinary Placement , Learning , Information Technology
17.
Article in Spanish | PAHO-IRIS | ID: phr-55431

ABSTRACT

[Extracto]. Al editor: Los autores queremos hacer un llamado de atención a la comunidad sobre un tema de salud pública que silenciosamente afecta a todos los seres vivos. Se trata de la presencia de contaminantes emergentes (CE) (ej. plaguicidas, cosméticos, nanomateriales, fármacos, entre otros) en el medioambiente. Los CE se caracterizan por su persistencia, bioconcentración, bioacumulación, biomagnificación, y movilidad ambiental. Los efectos de los CE sobre la salud humana y otros seres vivos es motivo de estudio desde hace poco tiempo, por ello en latinoamérica mayormente no se dispone de normativa legal que regule este tema. En países como, Brasil, Canadá, España, Francia, Inglaterra, Portugal y Uruguay se han realizado investigaciones que determinan la presencia de algunos CE en la entrada y salida de las plantas depuradoras de aguas servidas, demostrándose que no es posible su completa eliminación. El problema radica en que se desconoce su toxicidad y la de sus metabolitos, que en ocasiones es mayor. Entre los CE detectados en estos estudios, destacan los siguientes fármacos: carbamazepina, atenolol, sulfadiazina, paracetamol, eritromicina, ácido salicílico, diclofenaco, ibuprofeno, 17 β-estradiol, progesterona y levonorgestrel.


Subject(s)
Drug Residues , Environmental Pollutants , Pharmacology , Environment and Public Health , Water Pollution , Water Pollution, Chemical , Drug Industry
18.
Edumecentro ; 13(4): 288-302, 2021.
Article in Spanish | LILACS | ID: biblio-1345963

ABSTRACT

RESUMEN Introducción: la Farmacología constituye el sustento científico de la terapéutica medicamentosa abordada en las asignaturas clínicas en la carrera de Estomatología, lo cual justifica su inclusión en los planes de estudios y pone de manifiesto la importancia de su enseñanza en la referida carrera. Objetivo: exponer algunas consideraciones esenciales sobre la enseñanza de la Farmacología en la carrera de Estomatología en Cuba. Métodos: se asumió como método general de investigación el dialéctico-materialista y de manera particular, los métodos de revisión documental (de los planes de estudios de la referida carrera, programas analíticos de la Farmacología y artículos científicos publicados en la base de datos SciELO), de análisis-síntesis para extraer los aspectos de mayor relevancia y el histórico-lógico. Desarrollo: la revisión documental realizada permitió el establecimiento de etapas que marcan el inicio y desarrollo de la enseñanza de la Farmacología en la carrera de Estomatología en Cuba; el análisis de ellas se realizó teniendo en cuenta los siguientes indicadores: ubicación curricular de la asignatura y características principales de su proceso enseñanza aprendizaje. Conclusiones: se revela como tendencia el tránsito desde una enseñanza con enfoque tradicionalista hacia una enseñanza con enfoque desarrollador y en consonancia con la educación médica superior contemporánea.


ABSTRACT Introduction: Pharmacology constitutes the scientific basis for drug therapy addressed in clinical subjects in the Dentistry degree, which justifies its inclusion in the study plans and highlights the importance of its teaching in the aforementioned degree. Objective: to present some essential considerations on the teaching of Pharmacology in the Dentistry degree in Cuba. Methods: the dialectical-materialist method of investigation was assumed as a general method of investigation and in a particular way, the methods of documentary review (of the study plans of the aforementioned degree, analytical programs of Pharmacology and scientific articles published in the SciELO database) , of analysis-synthesis to extract the most relevant and historical-logical aspects. Development: the documentary review carried out allowed the establishment of stages that mark the beginning and development of the teaching of Pharmacology in the Dentistry degree in Cuba; its analysis was carried out taking into account the following indicators: curricular location of the subject and main characteristics of its teaching-learning process. Conclusions: the transition from teaching with a traditional approach to teaching with a developing one according to contemporary higher medical education is revealed as a trend.


Subject(s)
Pharmacology , Students, Dental , Program
19.
Nihon Yakurigaku Zasshi ; 156(6): 335-337, 2021.
Article in Japanese | MEDLINE | ID: mdl-34719564

ABSTRACT

Laboratory work is an essential part of natural science education because it provides students with a valuable opportunity to experience practical scientific research firsthand. In laboratory work in pharmacology, students generally learn about biological mechanisms and drug action mechanisms by analyzing drug actions using laboratory animals. Actual experience with hands and eyes is an important factor in the laboratory work. Under the COVID-19 epidemic, however, we were forced to conduct the laboratory work online. For the laboratory work using isolated organs, we used simulation software, in which students can examine effects of a range of drugs on the smooth muscle within the guinea pig ileum. For the behavioral observation practice, we showed the video of the experiments conducted by the instructors beforehand to the students, and asked them to observe and analyze the behavior. In this review, we will share our challenges to online laboratory work.


Subject(s)
COVID-19 , Pharmacology , Animals , Guinea Pigs , Humans , Laboratories , Learning , SARS-CoV-2
20.
Nihon Yakurigaku Zasshi ; 156(6): 364-369, 2021.
Article in Japanese | MEDLINE | ID: mdl-34719571

ABSTRACT

In vivo cardiovascular experiments as part of safety pharmacology studies have been developed for small molecule drug candidates to maximize detection power for potential undesirable pharmacodynamic effects of a drug candidate on physiological functions, and have been established with appropriate expertise. Conscious freely-moving telemeterized non-rodents are generally used for the in vivo cardiovascular experiments. The technology and evaluation best practices for the experiments have been optimized by multiple researchers and as a result, the experiments considerably contribute to the estimation of cardiovascular risks for humans. In addition, as described in ICH E14&S7B Q&A draft, non-clinical studies are gaining importance in the integrated risk assessment for QT prolongation in humans, and high quality data obtained in non-clinical studies are being required. This manuscript introduces actual technology and evaluation for in vivo cardiovascular safety pharmacology studies based on Japan activity for Improvement of Cardiovascular Evaluation by Telemetry system (J-ICET), which is one of the working groups hosted by Japanese Safety Pharmacology Society.


Subject(s)
Cardiovascular System , Drug-Related Side Effects and Adverse Reactions , Long QT Syndrome , Pharmacology , Drug Evaluation, Preclinical , Humans , Technology
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