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Biological Research Jul 2019Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote...
BACKGROUND
Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells.
METHODS
In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine.
RESULTS
Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3.
CONCLUSIONS
Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.
Topics: Anesthetics, Local; Apoptosis; Carcinoma, Hepatocellular; Caspase 3; Cell Line, Tumor; Cell Proliferation; Flow Cytometry; Humans; Liver Neoplasms; Microscopy, Confocal; Microscopy, Fluorescence; Mitochondria; Ropivacaine; Signal Transduction
PubMed: 31300048
DOI: 10.1186/s40659-019-0242-7 -
JAMA Psychiatry Feb 2020This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms.
OBJECTIVE
To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores from baseline to 8 weeks.
DESIGN, SETTING, AND PARTICIPANTS
This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only physicians performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist-Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months.
INTERVENTIONS
Paired right-sided SGB or sham procedures at weeks 0 and 2.
MAIN OUTCOMES AND MEASURES
Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori).
RESULTS
Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was -12.6 points (95% CI, -15.5 to -9.7 points) for the group receiving SGB treatments, compared with -6.1 points (95% CI, -9.8 to -2.3 points) for those receiving sham treatment (P = .01).
CONCLUSIONS AND RELEVANCE
In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03077919.
Topics: Anesthetics, Local; Animals; Autonomic Nerve Block; Double-Blind Method; Female; Humans; Injections; Male; Psychiatric Status Rating Scales; Ropivacaine; Stellate Ganglion; Stress Disorders, Post-Traumatic
PubMed: 31693083
DOI: 10.1001/jamapsychiatry.2019.3474 -
Anesthesiology Mar 2018
Topics: Arthroplasty, Replacement, Knee; Bupivacaine; Femur; Humans; Nerve Block; Ropivacaine
PubMed: 29438244
DOI: 10.1097/ALN.0000000000002034 -
Anaesthesia May 1991
Topics: Amides; Anesthesia, Conduction; Anesthetics, Local; Animals; Humans; Ropivacaine
PubMed: 2035775
DOI: 10.1111/j.1365-2044.1991.tb09537.x -
Theranostics 2023Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to...
Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8 T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8 T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8 T cells infiltration into tumor and potentiates PTT efficacy. This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.
Topics: Animals; Mice; Phototherapy; Hydrogels; Photothermal Therapy; Ropivacaine; CD8-Positive T-Lymphocytes; Imiquimod; Neoplasms; Indocyanine Green; Analgesics; Pain
PubMed: 37153743
DOI: 10.7150/thno.81325 -
International Journal of Nanomedicine 2022Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for...
INTRODUCTION
Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide.
METHODS
Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect.
RESULTS
Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which could be mineralized to form drug/peptide nanocrystals by adjusting the pH. Under physiological condition, the nanocrystals could release free ropivacaine slowly. As evaluated in rodent models, the anesthetic and analgesic effects of this formulation were significantly extended without causing toxicity.
CONCLUSION
Based on the interaction between ropivacaine and Q11, a controllable biomineralization process could be induced to obtain homogeneous nanocrystals, which could be used as an injectable long-acting analgesic formulation. This crystallization strategy utilizing the peptide-drug interaction also provided a promising pathway to fabricate long-acting formulations for many other small molecular drugs.
Topics: Amides; Analgesia; Anesthetics, Local; Humans; Pain, Postoperative; Peptides; Ropivacaine
PubMed: 35937079
DOI: 10.2147/IJN.S369706 -
Medicine Jun 2022To provide a basis for treating postherpetic neuralgia (PHN), we compared the efficacy of lidocaine and ropivacaine stellate ganglion block (SGB) in PHN treatment in the...
To provide a basis for treating postherpetic neuralgia (PHN), we compared the efficacy of lidocaine and ropivacaine stellate ganglion block (SGB) in PHN treatment in the upper limbs.Data from 252 patients with upper-limb PHN were retrospectively analyzed. The lidocaine group (n = 118) was treated with oral pregabalin capsules 75 mg twice a day, tramadol hydrochloride sustained release tablets 100 mg twice a day, and amitriptyline 25 mg once at night combined with ultrasound-guided lidocaine SGB; the ropivacaine group (n = 134) was orally administered the same medicines combined with ultrasound-guided ropivacaine SGB. The visual analog scale (VAS), self-rating anxiety scale (SAS), and adverse reactions were compared between the groups before treatment and at 1 week, 1 month, and 3 months after treatment.There were no significant differences between the lidocaine and ropivacaine groups in terms of sex, age, height, weight, and pain duration (P > .05). There was no significant difference between the groups in VAS and SAS scores before treatment (P > .05). At 1 week, 1 month, and 3 months after ultrasound-guided SGB treatment, the VAS and SAS scores were significantly lower in the ropivacaine group than in the lidocaine group (P < .05). There were no significant differences between the groups in terms of adverse reactions (P > .05).For ultrasound-guided SGB treatment of upper limb PHN, ropivacaine is superior to lidocaine. Ultrasound-guided ropivacaine SGB is safe and effective for the treatment of upper limb PHN.
Topics: Anesthetics, Local; Humans; Lidocaine; Neuralgia, Postherpetic; Retrospective Studies; Ropivacaine; Stellate Ganglion; Upper Extremity
PubMed: 35687777
DOI: 10.1097/MD.0000000000029394 -
Anesthesiology Nov 2018
Topics: Bupivacaine; Ropivacaine; Urinary Tract
PubMed: 30325811
DOI: 10.1097/ALN.0000000000002419 -
British Journal of Anaesthesia Feb 1996
Review
Topics: Amides; Anesthetics, Local; Humans; Ropivacaine
PubMed: 8777115
DOI: 10.1093/bja/76.2.300 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Nov 2021To investigate the effects and molecular mechanism of ropivacaine hydrochloride on osteosarcoma cell proliferation, invasion, and apoptosis. The osteosarcoma...
To investigate the effects and molecular mechanism of ropivacaine hydrochloride on osteosarcoma cell proliferation, invasion, and apoptosis. The osteosarcoma doxorubicin-resistant cell line (U2OS/DOX) was established by gradually increasing the drug doses. U2OS/DOX cells were treated with ropivacaine hydrochloride at the concentrations of 0, 20, 50 and 100 μg/ml, respectively; as different concentrations treatment groups of ropivacaine hydrochloride. pcDNA3.1 and pcDNA3.1-Livin were transfected into U2OS/DOX cells and then treated with 100 μg/ml ropivacaine hydrochloride, which were defined as ropivacaine hydrochloride 100 μg/ml+pcDNA3.1 group, ropivacaine hydrochloride 100 μg/ml+pcDNA3.1-Livin group. MTT was used to detect the cell proliferation inhibition rate and inhibitory concentration (IC). Western blot was used to detect the expressions of cyclin-dependent kinase inhibitor 1A (P21) and activated cysteine aspartic protease-3 (Cleaved Caspase-3), E-cadherin, matrix metalloproteinase 2 (MMP-2) and Livin; clone formation experiments were used to detect the number of cell clones formed; flow cytometry was used to detect apoptosis; Transwell was used to detect cell migration and invasion; real-time fluorescent quantitative PCR (RT-qPCR) was used to detect Livin mRNA expression. When the concentration of doxorubicin was more than 1 μg/ml, the proliferation inhibition rate of osteosarcoma cells U2OS was significantly increased in a concentration-dependent manner (<0.05); when the concentration of doxorubicin was more than 10 μg/ml, the proliferation inhibition rate of osteosarcoma resistant cell U2OS/DOX was significantly increased, and it was dose-dependent (<0.05). In U2OS/DOX cells treated with ropivacaine hydrochloride, the expressions of P21, Cleaved Caspase-3, and E-cadherin were increased significantly, the expression of MMP-2 was decreased significantly, the cell proliferation inhibition rate was increased significantly, the number of colony formation was decreased significantly, and the cells apoptosis rate was increased significantly, the number of cell migration and invasion was decreased significantly, and the expression of Livin was significantly reduced, in a concentration-dependent manner (<0.05). Overexpression of Livin partially reversed the inhibitory effect of ropivacaine hydrochloride on proliferation, migration, invasion, and promotion effect on apoptosis of cell U2OS/DOX. Ropivacaine hydrochloride can significantly inhibit the proliferation, migration and invasion of doxorubicin-resistant osteosarcoma cells, and significantly promote osteoma cell apoptosis. The mechanism may be related to Livin.
Topics: Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Humans; Matrix Metalloproteinase 2; Osteosarcoma; Ropivacaine
PubMed: 34821101
DOI: 10.12047/j.cjap.6082.2021.088