Arginase II Promotes Intervertebral Disc Degeneration Through Exacerbating Senescence and Apoptosis Caused by Oxidative Stress and Inflammation via the NF-κB Pathway.

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which imposes massive clinical and socioeconomic burdens. Previous studies have demonstrated that oxidative stress and inflammation-induced senescence and apoptosis of nucleus pulposus cells (NPCs) are the main cellular processes that cause IDD. Arginase II (ARG2), an enzyme involved in a variety of pathological processes, including cellular senescence, apoptosis, oxidative stress, and inflammation, has been shown to promote degeneration in several degenerative diseases, including osteoarticular diseases. Based on previous studies, we hypothesized that ARG2 deficiency might be conducive to the treatment of IDD by inhibiting the dyshomeostasis of the extracellular matrix (ECM), and the oxidative stress and inflammatory response-induced senescence and apoptosis via NF-κB. In this study, we found that ARG2 deficiency inhibited senescence and apoptosis of NPCs, and degeneration of the ECM induced by oxidative stress and the inflammatory response. Similar results were found with the selective NF-κB pathway inhibitor JSH-23. In contrast, overexpression of ARG2 had the opposite effect. Taken together, our results suggest that ARG2 deficiency prevents IDD via NF-κB, and may therefore, be a potential therapeutic strategy for IDD.

Effects of OPRM1 A118G polymorphism on epidural analgesia with fentanyl during labor: a meta-analysis.

BACKGROUND: Emerging evidence has shown that the most common polymorphism (A118G; rs1799971 A>G) in the µ-opioid receptor (OPRM1) gene may influence the response to labor analgesia, but individually published studies showed inconclusive results. OBJECTIVE: This meta-analysis aimed to derive a more precise estimation of the effects of the OPRM1 A118G polymorphism on epidural analgesia with fentanyl during labor. METHODS: A literature search was conducted on PubMed, Embase, Web of Science, and China BioMedicine databases before April 1st, 2013. The crude standardized mean difference (SMD) or odds ratio (OR) with 95% confidence interval (CI) was calculated. RESULTS: Six clinical studies were included with a total 838 women who received epidural analgesia with fentanyl during labor. The meta-analysis results indicated that women carrying the G allele (AG+GG) of the OPRM1 A118G polymorphism required less fentanyl doses to achieve adequate pain relief compared with those with the AA homozygote (SMD=-0.24, 95% CI [-0.44, -0.03], p=0.022). The 118G variant was associated with a decreased ED50 of fentanyl for labor analgesia (SMD=-1.56, 95% CI [-1.97, -1.15], p<0.001). The analgesia satisfaction in women carrying the G allele (AG+GG) was higher than those with the AA homozygote (SMD=0.22, 95% CI [0.05, 0.39], p=0.012). However, there were no statistically significant differences between an AA homozygote and a G carrier (AG+GG) in the incidence of nausea and vomiting (OR=1.99, 95% CI [0.88, 4.52], p=0.101). CONCLUSION: In conclusion, the current meta-analysis indicates that women carrying the G allele (AG+GG) of OPRM1 A118G polymorphism may have a good response to epidural analgesia with fentanyl during labor. The OPRM1 A118G polymorphism may help predict individuals' response to epidural labor analgesia and so optimize postoperative pain control.

Butorphanol prevents morphine-induced pruritus without increasing pain and other side effects: a systematic review of randomized controlled trials.

PURPOSE: Pruritus is a frequent adverse event after administration of morphine. Butorphanol has been used to prevent morphine-induced pruritus, but its efficacy is still controversial. The aim of this systematic review was to evaluate the efficacy of using butorphanol to prevent morphine-induced pruritus. SOURCE: We searched PubMed, Cochrane Library, EMBASE, and China's BioMedical Disc for full reports of randomized controlled trials that compared the use of butorphanol with either placebo or no treatment for preventing morphine-induced pruritus. The number of patients experiencing pruritus or other side effects was analyzed using relative risk (RR) with 95% confidence intervals (CI). PRINCIPAL FINDINGS: Sixteen trials (795 patients) were analyzed. Continuous intravenous and epidural butorphanol reduced pruritus with RR 0.22 (95% CI 0.10 to 0.45) and RR 0.24 (95% CI 0.16 to 0.36), respectively. Use of epidural butorphanol decreased the number of patients requesting rescue treatment for pruritus (RR 0.57; 95% CI 0.41 to 0.81). Butorphanol decreased postoperative pain intensity at four, eight, and 12 hr with standardized mean differences of -0.29 (95% CI -0.52 to -0.05), -0.30 (95% CI -0.56 to -0.04), and -0.23 (95% CI -0.46 to -0.01), respectively. Epidural but not intravenous butorphanol reduced postoperative nausea and vomiting (PONV) (RR 0.35; 95% CI 0.19 to 0.66). Butorphanol did not increase respiratory depression (RR 0.71; 95% CI 0.31 to 1.63), somnolence (RR 0.71; 95% CI 0.22 to 2.37), or dizziness (RR 2.45; 95% CI 0.35 to 17.14). CONCLUSION: Butorphanol administered with morphine may be an effective strategy for preventing morphine-induced pruritus as it decreases pain intensity and PONV without increasing other side effects. Thus, it can be recommended for preventing morphine-induced pruritus during the perioperative period.

Meta analysis of propranolol effects on gastrointestinal hemorrhage in cirrhotic patients.

AIM: To assess the effects of propranolol as compared with placebo on gastrointestinal hemorrhage and total mortality in cirrhotic patients by using meta analysis of 20 published randomized clinical trials. METHODS: A meta analysis of published randomized clinical trials was designed. Published articles were selected for study based on a computerized MEDLINE and a manual search of the bibliographies of relevant articles. Data from 20 relevant studies fulfilling the inclusion criteria were retrieved by means of computerized and manual search. The reported data were extracted on the basis of the intention-to-treat principle, and treatment effects were measured as risk differences between propranolol and placebo. Pooled estimates were computed according to a random-effects model. We evaluated the pooled efficacy of propranolol on the risk of gastrointestinal hemorrhage and the total mortality. RESULTS: A total of 1,859 patients were included in 20 trials, 931 in the propranolol groups and 928 as controls. Among the 652 patients with upper gastrointestinal tract hemorrhage, 261 patients were treated with propranolol, and 396 patients were treated with placebo or non-treated. Pooled risk differences of gastrointestinal hemorrhage were -18 % [95 % CI, -25 %, -10 %] in all trials, -11 % [95 % CI, -21 %, -1 %] in primary prevention trials, and -25 % [95 % CI, -39 %, -10 %] in secondary prevention trials. A total of 440 patients died, 188 in propranolol groups and 252 in control groups. Pooled risk differences of total death were -7 % [95 % CI, -12 %, -3 %] in all trials, -9 % [95 % CI, -18 %, -1 %] in primary prevention trials, and -5 % [95 % CI, -9 %, -1 %] in secondary prevention trials. CONCLUSION: Propranolol can markedly reduce the risks of both primary and recurrent gastrointestinal hemorrhage, and also the total mortality.