RESUMO
Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain.
RESUMO
Background: Heart failure is a common cardiovascular disease that imposes a heavy clinical and economic burden worldwide. Previous research and guidelines have supported exercise training as a safe, effective, and cost-efficient treatment to intervene in heart failure. The aim of this study was to analyze the global published literature in the field of exercise training for heart failure from 2002 to 2022, and to identify hot spots and frontiers within this research field. Methods: Bibliometric information on literature on the topic of exercise training for heart failure published between 2002 and 2022 was searched and collected in the Web of Science Core Collection. CiteSpace 6.1.R6 (Basic) and VOSviewer (1.6.18) were applied to perform bibliometric and knowledge mapping visualization analyses. Results: A total of 2017 documents were retrieved, with an upward-stable trend in the field of exercise training for heart failure. The US authors were in the first place with 667 documents (33.07%), followed by Brazilian authors (248, 12.30%) and Italian authors (182, 9.02%). The Universidade de São Paulo in Brazil was the institution with the highest number of publications (130, 6.45%). The top 5 active authors were all from the USA, with Christopher Michael O'Connor and William Erle Kraus publishing the most documents (51, 2.53%). The International Journal of Cardiology (83, 4.12%) and the Journal of Applied Physiology (78, 3.87%) were the two most popular journals, while Cardiac Cardiovascular Systems (983, 48.74%) and Physiology (299, 14.82%) were the two most popular categories. Based on the results of keyword co-occurrence network and co-cited reference network, the hot spots and frontiers of research in the field of exercise training for heart failure were high-intensity interval training, behaviour therapy, heart failure with preserved ejection fraction, and systematic reviews. Conclusion: The field of exercise training for heart failure has experienced two decades of steady and rapid development, and the findings of this bibliometric analysis provide ideas and references for relevant stakeholders such as subsequent researchers for further exploration.
RESUMO
A mild, efficient, and highly selective method for the synthesis of pyranoquinoline and furoquinoline derivatives via a three-component reaction of aromatic aldehyde, naphthalen-2-amine or anthracen-2-amine and 2,3-dihydrofuran, or 3,4-dihydro-2H-pyran catalyzed by iodine is described. It should be noted that exo-isomer was obtained with high selectivity in good yields, which was confirmed by X-ray diffraction analysis. The 3-arylbenzo(naphtha)[f]quinolines were isolated in high yields when the chain n-butylvinyl ether was used as reactant, with the unexpected loss of the butoxy group.
