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991.
Andrea J Vernall Stephen J Hill Barrie Kellam 《British journal of pharmacology》2014,171(5):1073-1084
The past decade has witnessed fluorescently tagged drug molecules gaining significant attraction in their use as pharmacological tools with which to visualize and interrogate receptor targets at the single-cell level. Additionally, one can generate detailed pharmacological information, such as affinity measurements, down to almost single-molecule detection limits. The now accepted utilization of fluorescence-based readouts in high-throughput/high-content screening provides further evidence that fluorescent molecules offer a safer and more adaptable substitute to radioligands in molecular pharmacology and drug discovery. One such drug-target family that has received considerable attention are the GPCRs; this review therefore summarizes the most recent developments in the area of fluorescent ligand design for this important drug target. We assess recently reported fluorescent conjugates by adopting a receptor-family-based approach, highlighting some of the strengths and weaknesses of the individual molecules and their subsequent use. This review adds further strength to the arguments that fluorescent ligand design and synthesis requires careful planning and execution; providing examples illustrating that selection of the correct fluorescent dye, linker length/composition and geographic attachment point to the drug scaffold can all influence the ultimate selectivity and potency of the final conjugate when compared with its unlabelled precursor. When optimized appropriately, the resultant fluorescent conjugates have been successfully employed in an array of assay formats, including flow cytometry, fluorescence microscopy, FRET and scanning confocal microscopy. It is clear that fluorescently labelled GPCR ligands remain a developing and dynamic research arena.Linked ArticlesThis article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-5 相似文献
992.
John J. Chen Sandy Hong Patricia A. Kirby Bruno A. Policeni Keith D. Carter Matthew J. Thurtell 《Neuro-ophthalmology (Aeolus Press)》2014,38(3):145-148
Wegener’s granulomatosis often affects the orbit, typically presenting with painful proptosis. The authors describe a 14 year-old girl, with limited Wegener’s granulomatosis, who initially presented with an isolated painless abduction deficit that spontaneously resolved over several weeks. She subsequently developed painful proptosis and diplopia, followed by facial and oral nodules. This case demonstrates that limited Wegener’s granulomatosis can rarely present with an isolated painless abduction deficit. 相似文献
993.
Andrea Nindler 《Zeitschrift für Psychodrama und Soziometrie》2014,13(1):51-66
The author presents her psychodramatic work with children and teenagers, confronted with death and grief. To begin with, aspects of death, grief and grief counseling are introduced. Then psychodramatic interventions and instructions of the “Care Box”, developed by the author for acute crisis situations of death and grief as well as grief counselling for children and teenagers, are presented. The material provided in the “Care-Box” has been chosen by psychodramatic criteria and is applicable like intermediary objects. Finally, rituals which can be conducted in the acute crisis situation and are also well adaptable in the continuative grief counselling, are presented. 相似文献
994.
Andrea Cavallo Cecilia Heyes Cristina Becchio Geoffrey Bird Caroline Catmur 《Social cognitive and affective neuroscience》2014,9(8):1082-1088
The human mirror system has been the subject of much research over the past two decades, but little is known about the timecourse of mirror responses. In addition, it is unclear whether mirror and counter-mirror effects follow the same timecourse. We used single-pulse transcranial magnetic stimulation to investigate the timecourse of mirror and counter-mirror responses in the human brain. Experiment 1 demonstrated that mirror responses can be measured from around 200 ms after observed action onset. Experiment 2 demonstrated significant effects of counter-mirror sensorimotor training at all timepoints at which a mirror response was found in Experiment 1 (i.e. from 200 ms onward), indicating that mirror and counter-mirror responses follow the same timecourse. By suggesting similarly direct routes for mirror and counter-mirror responses, these results support the associative account of mirror neuron origins whereby mirror responses arise as a result of correlated sensorimotor experience during development. More generally, they contribute to theorizing regarding mirror neuron function by providing some constraints on how quickly mirror responses can influence social cognition. 相似文献
995.
Prevalence of bleeding manifestations in 128 heterozygotes for Factor X deficiency,mainly for FX Friuli,matched versus 128 unaffected family members,during a long sequential observation period (23.5 years) 下载免费PDF全文
996.
Atrial Function Assessed by Speckle Tracking Echocardiography Is a Good Predictor of Postoperative Atrial Fibrillation in Elderly Patients 下载免费PDF全文
997.
A diaper bank and home visiting partnership: Initial exploration of research and policy questions 下载免费PDF全文
998.
Marcelo Leiva-Bianchi Francisco Ahumada Andrea Araneda Juan Botella 《Issues in mental health nursing》2018,39(4):320-327
The psychosocial impact concept improves the understanding of the effects of disasters on people and communities. However, its definition is not clear. This work explores consistencies between studies (k = 21) that refer to the psychosocial impact of disasters by way of a meta-analytic synthesis. This synthesis indicates that people are more prone to illness when they are exposed to a disaster, and less when they are protected (OR = 2.737). Please check the change conveys the intended meaning or amend Nevertheless, there are no differences in healthy responses, regardless of how protected or exposed they are (OR = 1.053). Finally, a model is proposed to explain four types of psychosocial impact: resilient, traumatic, sensitive, witness. 相似文献
999.
Giammaria Fiorentini Camillo Aliberti Donatella Sarti Paolo Coschiera Massimo Tilli Luca Mulazzani Paolo Giordani Francesco Graziano Alfonso Marqués Gonzalez Raul García Marcos Fernando Gómez Mugnoz Maurizio Cantore Stefano Ricci Vincenzo Catalano Andrea Mambrini 《World journal of gastrointestinal oncology》2015,7(6):47-54
AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases.METHODS: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m2 and then 250 mg/m2; good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS).RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy.CONCLUSION: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM. 相似文献
1000.
Bruno Revol Marie Joyeux‐Faure Marie‐Victoire Albahary Remy Gressin Michel Mallaret Jean‐Louis Pepin Sandrine H. Launois 《Fundamental & clinical pharmacology》2017,31(3):367-368
Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. 相似文献