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1.
Theranostics ; 10(16): 7034-7052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32641977

RESUMO

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.


Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Vacinas Virais/isolamento & purificação , Vacinas Virais/farmacologia , Betacoronavirus/química , Betacoronavirus/genética , Betacoronavirus/imunologia , Bioengenharia/métodos , Bioengenharia/tendências , Reatores Biológicos , Técnicas de Cultura de Células , Simulação por Computador , Infecções por Coronavirus/imunologia , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/tendências , Farmacorresistência Viral , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Modelos Biológicos , Organoides/citologia , Organoides/virologia , Pneumonia Viral/imunologia , Nanomedicina Teranóstica
3.
Nat Commun ; 11(1): 2685, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483209

RESUMO

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.


Assuntos
Ensaios Clínicos como Assunto/métodos , Filariose Linfática/tratamento farmacológico , Filaricidas/uso terapêutico , Oncocercose/tratamento farmacológico , Protocolos de Ensaio Clínico como Assunto , Ensaios Clínicos como Assunto/estatística & dados numéricos , Simulação por Computador , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/estatística & dados numéricos , Humanos , Ivermectina/uso terapêutico , Modelos Biológicos , Oncocercose/parasitologia , Oncocercose/transmissão
4.
Sanid. mil ; 75(3): 156-161, jul.-sept. 2019.
Artigo em Espanhol | IBECS | ID: ibc-187451

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento publicados en marzo y abril de 2018, considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in March, April and May of 2018, and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product


Assuntos
Humanos , Avaliação de Medicamentos/métodos , Equipamentos e Provisões/normas , Avaliação de Medicamentos/normas , Arginina/uso terapêutico , Buprenorfina/uso terapêutico , Antígenos CD34 , Cicloexanos , Lamivudina , Hidroxiureia , Toxinas Botulínicas Tipo A , Prestação Positiva de Saúde
5.
Endodoncia (Madr.) ; 37(2): 8-20, sept. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-186295

RESUMO

Objetivos. Los objetivos de este son: 1. Evaluar el consumo de medicamentos, así como la automedicación entre los individuos que acuden a realizarse una endodoncia. 2.Evaluar la mejoría de sintomatología tras la toma de medicación. 3. Evaluar la ansiedad dental entre los pacientes sometidos a tratamiento endodóntico previo a la intervención. Material y Métodos: Se realizó un estudio de tipo observacional, transversal y comparativo, consistente en una encuesta sobre pacientes mayores de 16 años que acudieron a una clínica universitaria odontológica. Resultados: Se recopilaron 167 encuestas entre septiembre de 2017 y marzo del 2018, siendo válidas 131 y no válidas 36, cuyos resultados más destacados fueron los siguientes: · Ingesta de antibióticos + analgésicos y/o AINES (40,6%)· Ingesta analgésicos y/o AINES (59,4%). Origen de esa medicación; 44,6% prescrita por el odontólogo, seguida del 42,7% que corresponde a la tomada por decisión propia, 10,8% al médico de cabecera, 2,7% a urgencias y 0% al farmacéutico y de origen homeopático. Media de ansiedad en la escala de 4,38. La media de ansiedad en mujeres: 5 y en hombres: 3,2 (p: 0.0066). Grupo con algún tipo de formación académica; media de ansiedad: 4,24 y grupo sin ningún estudio; media de ansiedad: 8,75 (p: 0.0144). Conclusiones: Los pacientes encuestados tenían una alta tendencia a la automedicación, utilizándose fundamentalmente analgésicos y/o AINES. Además, referían mejoría en el día de la intervención tras haber tomado algún tipo de medicamento. Los pacientes encuestados sufrieron un grado de ansiedad medio previo a la realización del tratamiento endodóntico


Objectives: The objectives of this study are: 1. To evaluate the consumption of medicines as well as self-medication among the individuals who undergo endodontics.2. To evaluate the improvement of symptoms after taking medication. 3. To evaluate dental anxiety among patients undergoing endodontic treatment prior to the intervention. Material and Methods: An observational, transversal and comparative study was carried out, consisting of a survey of patients over 16 years of age who attended a university dental clinic. Results: In this study 167 surveys were collected, between September 2017 and March 2018, with 131 valid and 36 invalid. Taking antibiotics + analgesics and/or NSAIDs (40.6%) and analgesics and/or NSAIDs (59.4%); Origin of that medication; 44.6% prescribed by the dentist, followed by the 42.7% prescribed by the dentist, 10.8% by the general practitioner, 2.7% by the emergency department and 0% by the pharmacist and homeopathic origin. Average anxiety on the 4.38 scale. Average anxiety in women: 5 and in men: 3.2 (p: 0.0066).Group with some type of academic training; mean anxiety: 4.24 and group without any study; mean anxiety: 8.75 (p: 0.0144). Conclusions: The patients surveyed had a high tendency to self-medication, mainly using analgesics and/or NSAIDs. They also reported improvement on the day of the intervention after having taken some type of medication. The patients surveyed suffered a medium degree of anxiety prior to the endodontic treatment


Assuntos
Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Automedicação/tendências , Ansiedade/psicologia , Endodontia/métodos , Avaliação de Medicamentos/métodos , Sobremedicalização , Estudos Transversais , Resistência a Medicamentos , Epidemiologia Descritiva , Pulpite/tratamento farmacológico , Inquéritos e Questionários
6.
Future Oncol ; 15(28): 3219-3232, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432695

RESUMO

Pharmacologic inhibition of the Hedgehog pathway significantly enhanced the sensitivity of leukemic cells to cytotoxic drugs. Glasdegib (PF-04449913; DAURISMO™) is a potent and selective oral inhibitor of the Hedgehog signaling pathway with clinical activity in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), particularly in combination with chemotherapy. The results of Phase Ib/II studies evaluating safety and efficacy of glasdegib combined with chemotherapy in previously untreated patients with AML or high-risk myelodysplastic syndrome have recently been published. In the BRIGHT AML 1003 study, glasdegib in combination with low-dose cytarabine (LDAC) was well tolerated and demonstrated a significant 54% reduction in mortality compared with LDAC for AML patients. In 2018, the US FDA approved glasdegib in combination with LDAC for the treatment of newly diagnosed patients with AML who are 75 years old or older or who have co-morbidities that preclude use of intensive induction chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Avaliação de Medicamentos/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Benzimidazóis/administração & dosagem , Citarabina/administração & dosagem , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Compostos de Fenilureia/administração & dosagem , Prognóstico , Taxa de Sobrevida
7.
Gene Expr ; 19(3): 199-214, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31340881

RESUMO

Testing drugs in isogenic rodent strains to satisfy regulatory requirements is insufficient for derisking organ toxicity in genetically diverse human populations; in contrast, advances in mouse genetics can help mitigate these limitations. Compared to the expensive and slower in vivo testing, in vitro cultures enable the testing of large compound libraries toward prioritizing lead compounds and selecting an animal model with human-like response to a compound. In the case of the liver, a leading cause of drug attrition, isolated primary mouse hepatocytes (PMHs) rapidly decline in function within current culture platforms, which restricts their use for assessing the effects of longer-term compound exposure. Here we addressed this challenge by fabricating mouse micropatterned cocultures (mMPCC) containing PMHs and 3T3-J2 murine embryonic fibroblasts that displayed 4 weeks of functions; mMPCCs created from either C57Bl/6J or CD-1 PMHs outperformed collagen/Matrigel™ sandwich-cultured hepatocyte monocultures by ∼143-fold, 413-fold, and 10-fold for albumin secretion, urea synthesis, and cytochrome P450 activities, respectively. Such functional longevity of mMPCCs enabled in vivo relevant comparisons across strains for CYP induction and hepatotoxicity following exposure to 14 compounds with subsequent comparison to responses in primary human hepatocytes (PHHs). In conclusion, mMPCCs display high levels of major liver functions for several weeks and can be used to assess strain- and species-specific compound effects when used in conjunction with responses in PHHs. Ultimately, mMPCCs can be used to leverage the power of mouse genetics for characterizing subpopulations sensitive to compounds, characterizing the degree of interindividual variability, and elucidating genetic determinants of severe hepatotoxicity in humans.


Assuntos
Avaliação de Medicamentos/métodos , Hepatócitos/citologia , Cultura Primária de Células/métodos , Adolescente , Animais , Células Cultivadas , Avaliação de Medicamentos/normas , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Cultura Primária de Células/normas , Especificidade da Espécie
8.
Ther Innov Regul Sci ; 53(5): 584-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31311309

RESUMO

Pediatric clinical trials are often requested according to specific age ranges. In the past and still today, these ages may correspond to developmental stages, such as newborn, infancy, childhood, and adolescence. Selection of ages for pediatric participation in medication studies should correspond to ages of rapid changes in pharmacokinetics and pharmacodynamics. Age-related changes in several enzymes involved in drug metabolism and glomerular filtration are described as examples of optimal ages for study of specific drugs according to their pathways of disposition.


Assuntos
Ensaios Clínicos como Assunto/métodos , Avaliação de Medicamentos/métodos , Adolescente , Distribuição por Idade , Fatores Etários , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Farmacocinética
9.
Sanid. mil ; 75(2): 94-97, abr.-jun. 2019.
Artigo em Espanhol | IBECS | ID: ibc-183711

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en diciembre de 2018, enero y febrero de 2019, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in December 2018, January and February of 2019 , and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product


Assuntos
Humanos , Avaliação de Medicamentos/métodos , Aprovação de Drogas/métodos , Avaliação de Medicamentos/instrumentação , Analgésicos
10.
Cells ; 8(5)2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137590

RESUMO

Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted therapies with remarkable efficacy are currently in use against various tumors. Thus, there is a need for in vitro functional-potency assays that can be used to test the efficacy of molecular targeted drugs and model complex interactions between immune cells and tumor cells to evaluate the potential for cancer immunotherapy. This study represents an in vitro evaluation of different classes of molecular targeted drugs, including small-molecule inhibitors, monoclonal antibodies, and an antibody-drug conjugate, using lung PDOs. We evaluated epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) inhibitors using a suitable high-throughput assay system. Next, the antibody-dependent cellular cytotoxicity (ADCC) activity of an anti-HER2 monoclonal antibody was evaluated to visualize the interactions of immune cells with PDOs during ADCC responses. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using PDOs. Our results demonstrate that the in vitro assay systems using PDOs were suitable for evaluating molecular targeted drugs under conditions that better reflect pathological conditions.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Avaliação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Organoides/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Biópsia , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Receptores ErbB/antagonistas & inibidores , Humanos , L-Lactato Desidrogenase/análise , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Receptor ErbB-2/antagonistas & inibidores
13.
Sanid. mil ; 75(1): 19-26, ene.-mar. 2019.
Artigo em Espanhol | IBECS | ID: ibc-183701

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por la comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en septiembre, octubre y noviembre de 2018. Se trata de opiniones técnicas positivas previas a la autorización y puesta en el mercado del medicamento


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in September, October and November of 2018, and considered of interest to the healthcare profesional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product


Assuntos
Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/normas , Antígenos de Superfície/análise , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Avaliação de Medicamentos/legislação & jurisprudência
14.
Artif Cells Nanomed Biotechnol ; 47(1): 524-539, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30784319

RESUMO

Nanotechnology has emerged strongly in most of the field of sciences at a tiny scale. At this size, atoms and molecules work differently and present a diversity of amazing and appealing applications. Pharmaceutical nanocarriers comprise nanoparticles, nanospheres, nanocapsules, nanoemulsion, nanoliposomes and nanoniosomes. The major objectives in designing nanocarriers are to manage particle size, surface properties as well as drug release in order to fulfil specific objectives. Hence, characterizations of nanocarriers are very critical to control their desired in vitro and in vivo behaviour. Nanocarriers are characterized by their size, morphology and surface charge, using highly advanced microscopic techniques as scanning electron microscopy, transmission electron microscopy and atomic force microscopy. Surface morphology and size are measured by electron microscopy while dynamic light scattering and photon-correlation spectroscopy are used to determine the particle size and size distribution. Colloidal stability is ascertained through zeta potential which is an indirect measure of the surface charge and differential scanning calorimetry is used to characterize particles and drug interaction. Further, binding and internalization of targeted carriers to the specific cells could be determined by cell uptake study. Biodistribution study of targeted nanocarriers is carried out and intracellular uptake and subcellular localization of the nanocarrier could be confirmed using confocal microscopy. This review covers all the aforementioned aspect related to in vitro and in vivo characterization of pharmaceutical nanocarriers.


Assuntos
Portadores de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação de Medicamentos/métodos , Nanopartículas , Coloides , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapêutico , Estabilidade de Medicamentos , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Tamanho da Partícula
15.
Toxicol Sci ; 168(1): 3-17, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30364994

RESUMO

Drug-induced gastrointestinal toxicities (GITs) rank among the most common clinical side effects. Preclinical efforts to reduce incidence are limited by inadequate predictivity of in vitro assays. Recent breakthroughs in in vitro culture methods support intestinal stem cell maintenance and continual differentiation into the epithelial cell types resident in the intestine. These diverse cells self-assemble into microtissues with in vivo-like architecture. Here, we evaluate human GI microtissues grown in transwell plates that allow apical and/or basolateral drug treatment and 96-well throughput. Evaluation of assay utility focused on predictivity for diarrhea because this adverse effect correlates with intestinal barrier dysfunction which can be measured in GI microtissues using transepithelial electrical resistance (TEER). A validation set of widely prescribed drugs was assembled and tested for effects on TEER. When the resulting TEER inhibition potencies were adjusted for clinical exposure, a threshold was identified that distinguished drugs that induced clinical diarrhea from those that lack this liability. Microtissue TEER assay predictivity was further challenged with a smaller set of drugs whose clinical development was limited by diarrhea that was unexpected based on 1-month animal studies. Microtissue TEER accurately predicted diarrhea for each of these drugs. The label-free nature of TEER enabled repeated quantitation with sufficient precision to develop a mathematical model describing the temporal dynamics of barrier damage and recovery. This human 3D GI microtissue is the first in vitro assay with validated predictivity for diarrhea-inducing drugs. It should provide a platform for lead optimization and offers potential for dose schedule exploration.


Assuntos
Diarreia/induzido quimicamente , Avaliação de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Células Epiteliais/fisiologia , Células Epiteliais/ultraestrutura , Células CACO-2 , Diferenciação Celular , Impedância Elétrica , Humanos , Preparações Farmacêuticas , Cultura Primária de Células
16.
Appl Health Econ Health Policy ; 17(1): 93-101, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30284150

RESUMO

BACKGROUND: Early awareness and alert systems have been established in many countries but evidence on their ability to accurately prioritize new medicines (for early assessment) is limited. OBJECTIVE: The purpose of this study was to assess whether the Swedish Early Awareness and Alert System identified and prioritized (i.e., produced early assessment reports for) new medicines that would go on to have substantial economic impact. METHODS: We adapted a study design commonly used in the assessment of diagnostic test accuracy. The prioritization made by the Swedish Early Awareness and Alert System prior to marketing authorization comprised the index test and the national drug sales data in the second year post-authorization served as the reference standard. All initial marketing authorization applications for medicinal products processed by the European Medicines Agency between 2010 and 2015 (study population) were classified using the index test and the reference standard. RESULTS: Two hundred and fifty-three new medicinal products processed by the European Medicines Agency comprised the study population. Of these, 71 were prioritized by the Swedish Early Awareness and Alert System and 21 were classified as having substantial economic impact. The sensitivity and positive predictive value were 76.2% and 22.5%, respectively. Subgroup analyses showed that the accuracy of prioritization, in terms of sensitivity, was 100% for antineoplastic/immunomodulating agents. CONCLUSIONS: The Swedish Early Awareness and Alert System identified all new medicines that would go on to have substantial economic impact and prioritized most of these medicines. Our findings provide reassurance to decision makers who rely on the outputs of the Swedish Early Awareness and Alert System to keep informed about new medicines. Moreover, this study also provides valuable insights to stakeholders willing to establish or evaluate their own early awareness and alert activities and systems.


Assuntos
Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/normas , Drogas em Investigação , Comércio , Coleta de Dados , Humanos , Suécia
17.
Sanid. mil ; 74(4): 236-247, oct.-dic. 2018.
Artigo em Espanhol | IBECS | ID: ibc-182306

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en mayo, junio y julio de 2018, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in May, June and July of 2018, and considered of interest to the healthcare professional, are reviewed here. These are positive technical reports prior to the authorization and placing on the market of the product


Assuntos
Avaliação de Medicamentos/métodos , Aprovação de Drogas , Avaliação de Medicamentos/normas , Programas Nacionais de Saúde/normas , Comercialização de Medicamentos
18.
Clin Neurophysiol ; 129(11): 2325-2332, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30248622

RESUMO

OBJECTIVES: Cognitive impairment models are used in clinical studies aimed at proving pharmacology of drugs being developed for Alzheimer's disease and other cognitive disorders. Due to rising interest in nicotinic agonists, we aimed to establish a method to monitor neurophysiological effects of modulating the nicotinic cholinergic system. METHODS: In a four-way cross-over study, eyes-closed rest EEG was recorded in 28 healthy subjects receiving mecamylamine-a nicotinic acetylcholine receptor (nAChR) antagonist, which induces temporary cognitive dysfunction in healthy subjects-with co-administration of placebo, nicotine or galantamine. RESULTS: Using machine learning to optimally contrast the effects of 30 mg of mecamylamine and placebo on the brain, we developed a nAChR index that consists of 10 EEG biomarkers and shows high classification accuracy (∼95% non-cross-validated, ∼70% cross-validated). Importantly, using the nAChR index, we demonstrate reversal of mecamylamine-induced neurophysiological effects due to 16 mg of galantamine as well as administering 21 mg of nicotine transdermally. CONCLUSIONS: Our findings indicate that the mecamylamine challenge model jointly with the nAChR index-a measure of the nicotinic EEG profile-could aid future proof-of-pharmacology studies to demonstrate effects of nicotinic cholinergic compounds. SIGNIFICANCE: This novel measure for quantifying nicotinic cholinergic effects on the EEG could serve as a useful tool in drug development of pro-cognitive compounds.


Assuntos
Ondas Encefálicas/efeitos dos fármacos , Avaliação de Medicamentos/métodos , Mecamilamina/farmacologia , Antagonistas Nicotínicos/farmacologia , Nootrópicos/farmacologia , Adolescente , Adulto , Inibidores da Colinesterase/farmacologia , Cognição/efeitos dos fármacos , Avaliação de Medicamentos/normas , Galantamina/farmacologia , Humanos , Aprendizado de Máquina , Masculino , Mecamilamina/administração & dosagem , Mecamilamina/efeitos adversos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/administração & dosagem , Antagonistas Nicotínicos/efeitos adversos , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos
19.
Sanid. mil ; 74(3): 163-167, jul.-sept. 2018.
Artigo em Espanhol | IBECS | ID: ibc-182294

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento publicados en marzo y abril de 2018, considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in March, April and May of 2018, and considered of interest to the healthcare profesional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product


Assuntos
Humanos , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/normas , Resultado do Tratamento , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Rilpivirina , Infliximab , Anticorpos Monoclonais , Sufentanil , Trastuzumab
20.
Int J Clin Pharm ; 40(5): 1059-1071, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30117081

RESUMO

Background Continual evolution of resistance among bacteria against methods of surgical prophylaxis may make currently used beta-lactam regimens inadequate. Objective To re-evaluate beta-lactam regimens in surgical prophylaxis. Setting A pharmacodynamic Monte Carlo simulation (MCS) model based on a number of patients in China. Methods Pharmacodynamic profiling using Monte Carlo simulation up to 4 hours postinfusion was conducted for standard-dose, short-term (0.5 h) and prolonged (2 to 4 h) infusions of ampicillin, cefazolin, cefotaxime, cefoxitin, cefuroxime, ertapenem, and piperacillin/tazobactam in adult patients with normal renal function. Microbiological data were incorporated. Cumulative fraction of response (CFR) was determined for each regimen against populations of S. aureus, coagulase-negative staphylococci and E. coli. The optimal CFR was defined as ≥ 90% response. Main Outcome Measure Cumulative fractions of response of pharmacodynamic target attainment. Results During the first 2 hours postinfusion, piperacillin/tazobactam 3.375 g exhibited consistently optimal cumulative fractions against S. aureus, CoNS and E. coli. Ampicillin 2 g (2 h) also displayed optimal CFRs for S. aureus and E. coli but not for coagulase-negative staphylococci. Cefoxitin 2 g didnot achieve any optimal CFRs, even via 2-h prolonged infusion (maximum 72.8% CFR for S. aureus and 64.5% CFR for E. coli). Cefazolin 2 g (4 h) and cefuroxime 1.5 g (4 h) provided desired CFRs across 4 h postinfusion for S. aureus but provided poor CFRs for coagulase-negative staphylococci and E. coli. Only ertapenem 1 g for E. coli and S. aureus and cefotaxime 1 g for E. coli consistently yielded ≥ 90% CFRs for 4 hour postinfusion. Conclusions Certain dosing regimens may warrant adjustment for improved prevention efficiency and enhanced empirical antibiotic regimens for surgical prophylaxis.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/estatística & dados numéricos , Modelos Biológicos , Infecção da Ferida Cirúrgica/prevenção & controle , beta-Lactamas/administração & dosagem , Administração Intravenosa , Antibioticoprofilaxia/métodos , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/estatística & dados numéricos , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Método de Monte Carlo , Staphylococcus aureus/efeitos dos fármacos
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