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2.
Int J Radiat Biol ; 96(2): 167-171, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31702416

RESUMO

The 16th International Congress of Radiation Research (ICRR2019) was held in Manchester, UK, in August 2019. The Congress, which is held every four years, covered a wide spectrum of topics relevant for all aspects of radiation research including basic mechanisms, translational research, radiotherapy and health effects, and ecology. Here, we provide a report of the plenary and keynote talks presented at the meeting.


Assuntos
Radioterapia/métodos , Pesquisa Médica Translacional/métodos , Encéfalo/efeitos da radiação , Radiação Cósmica , DNA/efeitos da radiação , Dano ao DNA , Reparo do DNA , Humanos , Comunicação Interdisciplinar , Cooperação Internacional , Neoplasias/radioterapia , Radioterapia/tendências , Pesquisa Médica Translacional/tendências , Reino Unido
3.
J Ethnopharmacol ; 247: 112255, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31568819

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant. MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019. RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom. CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.


Assuntos
Etnofarmacologia/métodos , Medicina Tradicional/métodos , Piper/química , Extratos Vegetais/farmacologia , Pesquisa Médica Translacional/métodos , Etnofarmacologia/tendências , Humanos , Índia , Malásia , Extratos Vegetais/uso terapêutico , Singapura , Pesquisa Médica Translacional/tendências
6.
Biomed Res Int ; 2019: 8397521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828134

RESUMO

Retinal ganglion cell (RGC) death is the central and irreversible endpoint of optic neuropathies. Current management of optic neuropathies and glaucoma focuses on intraocular pressure-lowering treatment which is insufficient. As such, patients are effectively condemned to irreversible visual impairment. This review summarizes experimental treatments targeting RGCs over the last decade. In particular, we examine the various treatment modalities and determine their viability and limitations in translation to clinical practice. Experimental RGC treatment can be divided into (1) cell replacement therapy, (2) neuroprotection, and (3) gene therapy. For cell replacement therapy, difficulties remain in successfully integrating transplanted RGCs from various sources into the complex neural network of the human retina. However, there is significant potential for achieving full visual restoration with this technique. Neuroprotective strategies, in the form of pharmacological agents, nutritional supplementation, and neurotrophic factors, are viable strategies with encouraging results from preliminary noncomparative interventional case series. It is important to note, however, that most published studies are focused on glaucoma, with few treating optic neuropathies of other etiologies. Gene therapy, through the use of viral vectors, has shown promising results in clinical trials, particularly for diseases with specific genetic mutations like Leber's hereditary optic neuropathy. This treatment technique can be further extended to nonhereditary diseases, through transfer of genes promoting cell survival and neuroprotection. Crucially though, for gene therapy, teratogenicity remains a significant issue in translation to clinical practice.


Assuntos
Atrofia Óptica Hereditária de Leber/terapia , Doenças do Nervo Óptico/terapia , Células Ganglionares da Retina/transplante , Pesquisa Médica Translacional/tendências , Animais , Terapia Baseada em Transplante de Células e Tecidos/tendências , Modelos Animais de Doenças , Terapia Genética/tendências , Glaucoma/genética , Glaucoma/patologia , Glaucoma/terapia , Humanos , Fármacos Neuroprotetores/uso terapêutico , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/patologia , Doenças do Nervo Óptico/genética , Doenças do Nervo Óptico/patologia , Retina/patologia , Células Ganglionares da Retina/patologia
7.
Semin Reprod Med ; 37(3): 119-124, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31869839

RESUMO

Kisspeptin and neurokinin B (NKB) are hypothalamic neuropeptides that are vital for reproductive health. An absence of either kisspeptin or NKB signaling results in hypogonadotrophic hypogonadism and a failure to proceed through puberty. In recent years, several studies have demonstrated potential avenues for the clinical utility of medications that act through these pathways in the assessment and treatment of reproductive disorders. Kisspeptin acts to stimulate hypothalamic gonadotrophic-releasing hormone (GnRH) secretion from the hypothalamus. Kisspeptin induces gonadotrophin secretion in both healthy men and women, and in women with reproductive disorders such as hypothalamic amenorrhea (HA). Kisspeptin-based treatments hold promise for use during in vitro fertilization (IVF) treatment; a bolus of kisspeptin-54 induces an LH surge of 12 to 14 hours of duration sufficient to induce oocyte maturation, but with markedly reduced rates of the most significant complication of IVF treatment, ovarian hyperstimulation syndrome (OHSS). Kisspeptin could also be used chronically to restore reproductive health in patients with functional hypogonadism, such as those with HA. Furthermore, kisspeptin has potential as a diagnostic test of hypothalamic function; a "kisspeptin test" could be used in children with delayed puberty to identify the subset with genetically determined deficits in hypothalamic pathways (congenital hypogonadotrophic hypogonadism [CHH]). In addition to its role in hypothalamic GnRH pulse generation, NKB plays a critical role in the occurrence of one of the most troubling symptoms of the menopause, the "hot flush." Neurokinin-3 receptor (NK3R) antagonists are highly effective as treatments for hot flushes in postmenopausal women, with several compounds now in late-phase development. Furthermore, NK3R antagonism leads to a reduction in LH secretion by reducing GnRH pulsatility in the hypothalamus and has been shown to reduce androgen levels in women with polycystic ovary syndrome (PCOS) (in whom GnRH pulsatility is often increased). In summary, although further detailed evaluation in several clinical settings is ongoing, medications based on kisspeptin and NKB pathways have prodigious potential in the assessment and treatment of reproductive disorders.


Assuntos
Kisspeptinas/fisiologia , Neurocinina B/fisiologia , Pesquisa Médica Translacional , Animais , Feminino , Fertilização In Vitro/métodos , Fertilização In Vitro/tendências , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Hipotálamo/metabolismo , Masculino , Reprodução/fisiologia , Pesquisa Médica Translacional/métodos , Pesquisa Médica Translacional/tendências
8.
Adv Exp Med Biol ; 1168: 1-7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31713161

RESUMO

The diagnosis, prognosis and treatment of cancer has had a great improvement due to the "omics" technologies such as genomics, proteomics, epigenomics, pharmacogenomics, and metabolomics. The technological progress of these technologies has allowed precision medicine to become a clinical reality. The study of different biomolecules such as DNA, RNA and proteins has helped to detect alterations in genes, changes in gene expression profiles and loss or gain of protein function, which allows us to make associations and better understand the cancer biology. Data obtained from different "omics" technologies gives a complementary spectrum of information that helps us to understand and unveil new information for a better diagnosis, prognosis, prediction of new molecular targets of anticancer therapies, etc. This chapter presents a general landscape of the interaction between the Pharmaco-Geno-Proteo-Metabolomic and translational medicine research in cancer.


Assuntos
Metabolômica , Neoplasias , Farmacogenética , Proteômica , Pesquisa Médica Translacional , Humanos , Metabolômica/tendências , Neoplasias/fisiopatologia , Farmacogenética/tendências , Proteômica/tendências , Pesquisa Médica Translacional/tendências
9.
Adv Exp Med Biol ; 1168: 31-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31713163

RESUMO

Epigenomics refers to the study of genome-wide changes in epigenetic mechanisms including DNA methylation, histone modifications and non-coding RNAs expression. The alterations in normal DNA methylation and histone acetylation/deacetylation patterns lead to deregulated transcription and chromatin organization resulting in altered gene expression profiles that facilitates tumor development and progression. In consequence, novel therapeutic strategies aimed at reversing aberrant epigenetic marks in cancer cells have been developed and used in recent molecular studies and clinical trials. Pharmaco-epigenomics is a research area, which refers to the study of epigenome changes in cancer development and how chemotherapeutic agents can reverse these aberrant epigenetic marks by targeting the epigenetic machinery. Besides, the effects of genome-wide polymorphisms in populations leading to variations in drug response are also study subject of pharmaco-epigenomics and are being studied extensively in cancer. Recent findings showed that drug response could be largely influenced by the presence of aberrant epigenetic marks of the whole genome. This implies that biological pathways and cellular processes are under the impact of epigenome status. However, data about the relationship between drug response and the epigenomic variations is still scarce mainly because the epigenome is highly variable between individuals. The present chapter reviewed the advances on the epigenetics changes mainly DNA methylation and histones modifications on cervical and breast human cancers. A special emphasis in how they could be used as targets for the development and use of novel drugs in cancer therapy is delineated.


Assuntos
Epigenômica , Farmacogenética , Pesquisa Médica Translacional , Metilação de DNA , Epigenômica/tendências , Humanos , Neoplasias/fisiopatologia , Neoplasias/terapia , Farmacogenética/tendências , Pesquisa Médica Translacional/tendências
11.
PLoS Biol ; 17(10): e3000416, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600189

RESUMO

Fundamental scientific advances can take decades to translate into improvements in human health. Shortening this interval would increase the rate at which scientific discoveries lead to successful treatment of human disease. One way to accomplish this would be to identify which advances in knowledge are most likely to translate into clinical research. Toward that end, we built a machine learning system that detects whether a paper is likely to be cited by a future clinical trial or guideline. Despite the noisiness of citation dynamics, as little as 2 years of postpublication data yield accurate predictions about a paper's eventual citation by a clinical article (accuracy = 84%, F1 score = 0.56; compared to 19% accuracy by chance). We found that distinct knowledge flow trajectories are linked to papers that either succeed or fail to influence clinical research. Translational progress in biomedicine can therefore be assessed and predicted in real time based on information conveyed by the scientific community's early reaction to a paper.


Assuntos
Bibliometria , Pesquisa Biomédica/tendências , Aprendizado de Máquina , Pesquisa Médica Translacional/tendências , Ensaios Clínicos como Assunto , Humanos , Publicações Periódicas como Assunto , Guias de Prática Clínica como Assunto , Fatores de Tempo
13.
Am J Respir Cell Mol Biol ; 61(4): 429-439, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31573338

RESUMO

The University of Vermont Larner College of Medicine, in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), the Alpha-1 Foundation, the American Thoracic Society, the Cystic Fibrosis Foundation, the European Respiratory Society, the International Society for Cell & Gene Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop titled "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases" from July 24 through 27, 2017, at the University of Vermont, Burlington, Vermont. The conference objectives were to review and discuss current understanding of the following topics: 1) stem and progenitor cell biology and the role that they play in endogenous repair or as cell therapies after lung injury, 2) the emerging role of extracellular vesicles as potential therapies, 3) ex vivo bioengineering of lung and airway tissue, and 4) progress in induced pluripotent stem cell protocols for deriving lung cell types and applications in disease modeling. All of these topics are research areas in which significant and exciting progress has been made over the past few years. In addition, issues surrounding the ethics and regulation of cell therapies worldwide were discussed, with a special emphasis on combating the growing problem of unproven cell interventions being administered to patients with lung diseases. Finally, future research directions were discussed, and opportunities for both basic and translational research were identified.


Assuntos
Bioengenharia , Terapia Baseada em Transplante de Células e Tecidos , Pneumopatias/terapia , Células-Tronco , Bioengenharia/tendências , Terapia Baseada em Transplante de Células e Tecidos/ética , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Baseada em Transplante de Células e Tecidos/tendências , Ensaios Clínicos como Assunto , Vesículas Extracelulares/transplante , Previsões , Prioridades em Saúde , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/transplante , Colaboração Intersetorial , Pulmão/citologia , Pesquisa , Empresa de Pequeno Porte , Nicho de Células-Tronco , Engenharia Tecidual/métodos , Engenharia Tecidual/tendências , Pesquisa Médica Translacional/tendências
15.
Adv Parasitol ; 105: 69-93, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31530396

RESUMO

From the time it was conceptualized in 1998 to the present, RNAS+ has largely concentrated on research that will generate results to facilitate control, prevention and elimination of its target diseases. Diagnostics has remained an active field of research in order to develop tools that are appropriate for each stage from the first efforts until attempts to block transmission. For example, with regard to schistosomiasis, chemotherapy has excellent impact on morbidity, while better diagnostics and vaccine research have been promoted to complement the other components of the control programme. The need for surveillance in areas where the prevalence has been brought down to very low levels necessitated development of spatio-temporal tools and ecological models based on geographical information systems (GIS) to produce risk and distribution maps for monitoring and evaluation of programme success. New knowledge and experiences in management of the diseases contribute to the formulation of new schemes in management and treatment. Ways of drawing attention to the disease, such as determining disability weights for use in computation of burden of disease, updating epidemiological profile and unravelling new aspects of the disease provide bases for modifying the operation of control programmes as we move forward. Programme evaluation based on reports of actual implementation of activities brought to the fore problems related to the distribution of chemotherapy as well as social, cultural and behavioural aspects of endemic communities. Importantly, this highlighted the necessity of adapting control activities to specific situations of the endemic areas. New models evolving from reviews of this kind and success stories, such us the elimination of lymphatic filariasis (LF) in PR China and Cambodia are presented.


Assuntos
Serviços Preventivos de Saúde/tendências , Esquistossomose/prevenção & controle , Pesquisa Médica Translacional/tendências , Animais , Humanos , Serviços Preventivos de Saúde/normas , Esquistossomose/diagnóstico , Esquistossomose/tratamento farmacológico , Esquistossomose/transmissão
16.
Rev. psiquiatr. salud ment. (Barc., Ed. impr.) ; 12(3): 187-195, jul.-sept. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-187012

RESUMO

Pese al éxito (o consenso) conseguido en la homogeneización de criterios clínicos por los sistemas de clasificación psiquiátrica categoriales (DSM y CIE), su validez y utilidad, clínica y en investigación, son cuestionables. En este artículo de revisión presentamos el marco Criterios de Investigación por Dominios (Research Domain Criteria, RDoC) como una alternativa para la investigación traslacional en psiquiatría. El marco de investigación traslacional RDoC sistematiza dianas y métodos de investigación en psiquiatría. RDoC parte de un catálogo de bases neurofuncionales de la conducta y plantea la psicopatología como la expresión fenotípica de las alteraciones en dichas funciones. Estas se clasifican en 5sistemas psicobiológicos. Los constructos funcionales se validan mediante evidencia proveniente de estudios básicos en 7 niveles de análisis: genes, moléculas, células, circuitos nerviosos, fisiología, conducta y autoinformes. Frente a los sistemas categoriales centrados en el diagnóstico, RDoC propone centrar el estudio de la psicopatología como correlato de alteraciones funcionales detectables, biológicas y comportamentales. RDoC es un marco de investigación que vincula el sustrato biológico con las manifestaciones fenotípicas, para llegar a una nosología psiquiátrica útil para guiar el tratamiento. Pese a que los hallazgos de RDoC no articulan un modelo concreto de guía para la práctica clínica, es un sistema de transición útil para crear hipótesis de investigación clínica, básica y epidemiológica


Despite the consensus achieved in the homogenization of clinical criteria by categorical psychiatric classification systems (DEM and CIE), they are criticized for a lack of validity and inability to guide clinical treatment and research. In this review article we introduce the Research Domain Criteria (RDoC) framework as an alternative framework for translational research in psychiatry. The RDOC framework systematizes both research targets and methodology for research in psychiatry. RDoC is based on a catalogue of neurobiological and neurocognitive evidence of behaviour, and conceives psychopathology as the phenotypic expression of alterations of functional domains that are classified into 5psychobiological systems. The RdoC framework also proposes that domains must be validated with evidence in 7levels of analysis: genes, molecules, cells, nerve circuits, physiology, behaviour and self-reports. As opposed to categorical systems focused on diagnosis, RDoC focuses on the study of psychopathology as a correlate of detectable functional, biological and behavioural disruption of normal processes. In order to build a useful psychiatric nosology for guiding clinical interventions, the RDoC research framework links the neurobiological basis of mental processes with phenotypical manifestations. Although the RDoC findings have not yet been articulated into a specific model for guiding clinical practice, they provide a useful transition system for creating clinical, basic and epidemiological research hypotheses


Assuntos
Humanos , Pesquisa Médica Translacional/tendências , Psiquiatria/tendências , Transtornos Mentais/classificação , Domínios Científicos , Padrões de Prática Médica/tendências , Manual Diagnóstico e Estatístico de Transtornos Mentais
17.
Hum Genomics ; 13(1): 39, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455423

RESUMO

The field of pharmacogenomics (PGx) is gradually shifting from the reactive testing of single genes toward the proactive testing of multiple genes to improve treatment outcomes, reduce adverse events, and decrease the burden of unnecessary costs for healthcare systems. Despite the progress in the field of pharmacogenomics, its implementation into routine care has been slow due to several barriers. However, in recent years, the number of studies on the implementation of PGx has increased, all providing a wealth of knowledge on different solutions for overcoming the obstacles that have been emphasized over the past years. This review focuses on some of the challenges faced by these initiatives, the solutions and different approaches for testing that they suggest, and the evidence that they provide regarding the benefits of preemptive PGx testing.


Assuntos
Tomada de Decisão Clínica/métodos , Farmacogenética/tendências , Medicina de Precisão/tendências , Sistemas de Apoio a Decisões Clínicas/tendências , Assistência à Saúde/tendências , Humanos , Pesquisa Médica Translacional/tendências , Resultado do Tratamento
19.
Nature ; 572(7767): 43-50, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31367027

RESUMO

Science fiction notions of altering problematic memories are starting to become reality as techniques emerge through which unique memories can be edited. Here we review memory-editing research with a focus on improving the treatment of psychopathology. Studies highlight two windows of memory vulnerability: initial storage, or consolidation; and re-storage after retrieval, or reconsolidation. Techniques have been identified that can modify memories at each stage, but translating these methods from animal models to humans has been challenging and implementation into clinical therapies has produced inconsistent benefits. The science of memory editing is more complicated and nuanced than fiction, but its rapid development holds promise for future applications.


Assuntos
Memória/fisiologia , Psicopatologia/métodos , Pesquisa Médica Translacional/métodos , Animais , Humanos , Consolidação da Memória/fisiologia , Rememoração Mental/fisiologia , Modelos Animais , Psicopatologia/tendências , Pesquisa Médica Translacional/tendências
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