Search

Objective: To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo., Methods: We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval., Results: Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events., Conclusion: Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases., Competing Interests: The authors have declared that no competing interests exist.

Epilepsy is one of the most common neurological disorders, yet its treatment remains unsatisfactory. Saikosaponin a (SSa), a triterpene saponin derived from Bupleurum chinensis DC., has been demonstrated to have significant antiepileptic activity in a variety of epilepsy models in vivo. However, the electrophysiological activities and mechanisms of the antiepileptic properties of SSa remain unclear. In this study, whole-cell current-clamp recordings were used to evaluate the anticonvulsant activities of SSa in the hippocampal neuronal culture (HNC) models of acquired epilepsy (AE) and status epilepticus (SE). Whole-cell voltage-clamp recordings were used to evaluate the modulation effects of SSa on NMDA-evoked current and sodium currents in cultured hippocampal neurons. We found that SSa effectively terminated spontaneous recurrent epileptiform discharges (SREDs) in the HNC model of AE and continuous epileptiform high-frequency bursts (SE) in the HNC model of SE, in a concentration-dependent manner with an IC(50) of 0.42 µM and 0.62 µM, respectively. Furthermore, SSa significantly reduced the peak amplitude of NMDA-evoked current and the peak current amplitude of I(NaP). These results suggest for the first time that the inhibitions of NMDA receptor current and I(NaP) may be the underlying mechanisms of SSa's anticonvulsant properties, including the suppression of SREDs and SE in the HNC models of AE and SE. In addition, effectively abolishing the refractory SE implies that SSa may be a potential anticonvulsant candidate for the clinical treatment of epilepsy.

In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP)). The I(NaP) is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I(NaP) in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I(NaP), also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I(NaP) was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I(NaP) without affecting the transient sodium current (I(NaT)). Taken together, these results demonstrate for the first time that the I(NaP) blocker riluzole selectively inhibits I(NaP) and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I(NaP) of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.