-
Medicine Mar 2023Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with edaravone injection (ERI) for the treatment of acute cerebral infarction is not well determined. Therefore, we evaluated the efficacy of ERI combined with SXN versus that of ERI alone in patients with acute cerebral infarction.
METHODS
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases were searched up to July 2022. Randomized controlled trials comparing the outcomes of efficacy rate, neurologic impairment, inflammatory factors, and hemorheology were included. Odds ratio or standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to present the overall estimates. The quality of the included trials was evaluated by the Cochrane risk of bias tool. The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses.
RESULTS
Seventeen randomized controlled trials were included consisting of 1607 patients. Compared to ERI alone, treatment with ERI plus SXN had a greater effective rate than ER alone (odds ratio = 3.94; 95% CI: 2.85, 5.44; I2 = 0%, P < .00001), a lower National Institute of Health Stroke Scale (SMD= -1.39; 95% CI: -1.73, -1.05; I2 = 71%, P < .00001), lower neural function defect score (SMD= -0.75; 95% CI: -1.06,-0.43; I2 = 67%, P < .00001), and lower level of neuron-specific enolase (SMD= -2.10; 95% CI: -2.85, -1.35; I2 = 85%, P < .00001). ERI plus SXN treatment provided significant improvements in whole blood high shear viscosity (SMD = -0.87; 95% CI: -1.17, -0.57; I2 = 0%, P < .00001), and whole blood low shear viscosity (SMD = -1.50; 95% CI: -1.65, -1.36; I2 = 0%, P < .00001) compared to ERI alone.
CONCLUSION
ERI plus SXN showed better efficacy than ERI alone for patients with acute cerebral infarction. Our study provides evidence supporting the application of ERI plus SXN for acute cerebral infarction.
Topics: Humans; Edaravone; Stroke; Brain Ischemia; Acute Disease; Cerebral Infarction
PubMed: 36862906
DOI: 10.1097/MD.0000000000032929 -
Drug Design, Development and Therapy 2023Bone dysfunction is a crucial problem that occurs during rheumatoid arthritis (RA) disease. Osteoclast plays a significant role in bone resorption and osteoclast...
BACKGROUND
Bone dysfunction is a crucial problem that occurs during rheumatoid arthritis (RA) disease. Osteoclast plays a significant role in bone resorption and osteoclast differentiation and its enhancement of bone destruction. Edaravone remarkably exhibited free radical scavenging and anti-inflammatory effects. The objective of the current investigation is to comfort the inhibitory effect of Edaravone (ED) against complete Freund adjuvant (CFA) rat model via inhibition of angiogenesis and inflammation.
METHODS
Subcutaneous injection of CFA (1%) was used to induce arthritis; the rats were divided into different groups and received the oral administration of ED. Paw edema, body weight, and arthritis score were regularly estimated. Biochemical parameters were estimated, respectively. We also estimate the level of hypoxia-inducible factor-1α (HIF-1α), angiopoietin 1 (ANG-1), and vascular endothelial growth factor (VEGF). We also checked into how ED affected the differentiation of osteoclasts utilising a co-culture system with monocytes and synovial fibroblasts in arthritis rats.
RESULTS
ED treatment significantly (P<0.001) suppressed the arthritis score and paw edema and improved the body weight. ED treatment significantly (P<0.001) altered the antioxidant parameters and pro-inflammatory cytokines: inflammatory mediator nuclear kappa B factor (NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E (PGE), respectively. Furthermore, ED treatment significantly (P<0.001) suppressed the level of ANG-1, HIF-1α, and VEGF, respectively. The results suggest that ED suppressed osteoclast differentiation and also decreased the level of cytokines and osteopontin (OPN), receptor activator for nuclear factor-κ B Ligand (RANKL) and macrophage colony stimulating factor (M-CSF) in the co-culture supernatant of monocytes and synovial fibroblasts.
CONCLUSION
Edaravone could mitigate CFA via inhibiting angiogenesis and inflammatory reactions, which may be linked with the HIF-1α-VEGF-ANG-1 axis and also enhance the bone destruction of murine arthritis via suppression of osteoclast differentiation and inflammatory reaction.
Topics: Rats; Mice; Animals; Osteoclasts; Vascular Endothelial Growth Factor A; Freund's Adjuvant; Edaravone; Angiopoietin-1; Hypoxia-Inducible Factor 1, alpha Subunit; Arthritis, Rheumatoid; Cytokines; Arthritis, Experimental
PubMed: 36845667
DOI: 10.2147/DDDT.S391606 -
JPMA. the Journal of the Pakistan... Feb 2023To evaluate the impact of hepcidin and ferritin in pathogenesis and prognosis of type 2 diabetes mellitus subjects taking only metformin or combined anti-glycaemic...
OBJECTIVE
To evaluate the impact of hepcidin and ferritin in pathogenesis and prognosis of type 2 diabetes mellitus subjects taking only metformin or combined anti-glycaemic agents.
METHODS
The observational case-control study was conducted at the Department of Physiology, Baqai Medical University, Karachi, from August 2019 to October 2020, and comprised subjects from both genders who categorised into equal groups as non-diabetic controls, newly-diagnosed type 2 diabetes mellitus patients without any treatment, type 2 diabetes mellitus patients with exposure to metformin only, type 2 diabetes mellitus patients taking oral hypoglycaemic agents along with metformin, type 2 diabetes mellitus patients taking only insulin, and type 2 diabetes mellitus patients taking insulin and oral hypoglycaemic agents. Fasting plasma glucose was determined using glucose oxidase-peroxidase method, glycated haemoglobin by high performance liquid chromatography, high-density lipoprotein and low-density lipoprotein by direct methods, cholesterol by cholesterol oxidase phenol 4-amino antipyrine peroxidase and triglycerides by glycerol phosphate oxidase-phenol 4-amino antipyrine peroxidase method. Serum levels of ferritin, insulin and hepcidin were evaluated using Enzyme-linked immunosorbent assay. Insulin resistance was assessed using homeostasis model assessment for insulin resistance. Data was analysed using SPSS 21.
RESULTS
Of the 300 subjects, there were 50(16.66%) in each of the 6 groups. Overall, there were 144(48%) males and 155(51.66%) females. The mean age was significantly lower in the control group 34.72±7.87 compared to all the diabetic groups (p<0.05), and the same was the case with respect to all the parameters (p<0.05) except high-density lipoprotein (p>0.05). Besides, hepcidin level was significantly higher in the control group (p<0.05). Ferritin levels were significantly increased in newly-diagnosed T2DM subjects compared to the controls (p<0.05) while all other groups showed decreased ferritin levels (p<0.05). Hepcidin gave inverse correlation with glycated haemoglobin only in diabetics taking only metformin (r = -0.27, p=0.05).
CONCLUSIONS
Anti-diabetes drugs not only addressed type 2 diabetes mellitus, but also reduced levels of ferritin and hepcidin that are found to play a role in diabetes development.
Topics: Humans; Female; Male; Metformin; Diabetes Mellitus, Type 2; Hepcidins; Insulin Resistance; Case-Control Studies; Glycated Hemoglobin; Pakistan; Hypoglycemic Agents; Insulin; Peroxidases
PubMed: 36800717
DOI: 10.47391/JPMA.6154 -
Materials (Basel, Switzerland) Jan 2023A new heterocyclic azo dye ligand (L) was synthesized by the combination of 4-amino antipyrine with 4-aminophenol. The new Cr(III), Mn(II), Fe(III), Co(II), Ni(II),...
A new heterocyclic azo dye ligand (L) was synthesized by the combination of 4-amino antipyrine with 4-aminophenol. The new Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) complexes were synthesized in excellent yields. The metal chelate structures were elucidated using elemental analyses, FT-IR, H-NMR, mass, magnetic moment, diffused reflectance spectral and thermal analysis (TG-DTG), and molar conductivity measurement. According to the FT-IR study, the azo dye ligand exhibited neutral tri-dentate behavior, binding to the metal ions with the azo N, carbonyl O, and protonated phenolic OH. The H-NMR spectral study of the Zn(II) complex supported the coordination of the zo dye ligand without proton displacement of the phenolic OH. Diffused reflectance and magnetic moment studies revealed the octahedral geometry of the complexes, as well as their good electrolytic nature, excepting the Zn(II) and Cd(II) complexes, which were nonelectrolytes, as deduced from the molar conductivity study. The theoretical calculations of optimized HOMO-LUMO energies, geometrical parameters, electronic spectra, natural atomic charges, 3D-plots of MEP, and vibrational wavenumbers were computed and elucidated using LANL2DZ and 6-311G (d, p) basis sets of density functional theory (DFT) with the approach of B3LYP DFT and TD-DFT methods. The ligand and complexes have been assayed for their antimicrobial activity and compared with the standard drugs. Most of the complexes have manifested excellent antimicrobial activity against various microbial strains. A molecular docking investigation was also performed, to acquire more information about the binding mode and energy of the ligand and its metal complexes to the receptor using molecular docking. Altogether, the newly created ligand and complexes showed positive antibacterial effects and are worth future study.
PubMed: 36769903
DOI: 10.3390/ma16030897 -
Journal of Managed Care & Specialty... Feb 2023Funding for this summary was contributed by Blue Cross Blue Shield of MA, California Healthcare Foundation, The Patrick and Catherine Weldon Donaghue Medical Research...
The effectiveness and value of AMX0035 and oral edaravone for amyotrophic lateral sclerosis: A summary from the Institute for Clinical and Economic Review's Midwest Comparative Effectiveness Public Advisory Council.
Funding for this summary was contributed by Blue Cross Blue Shield of MA, California Healthcare Foundation, The Patrick and Catherine Weldon Donaghue Medical Research Foundation, Arnold Ventures, and Kaiser Foundation Health Plan Inc., to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy Solutions, Express Scripts, Genentech/ Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health First, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer. Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, Sun Life Financial, uniQure, and United Healthcare. Mr Nikitin, Ms McKenna, Ms Richardson, and Drs Rind and Pearson are employed by ICER. Through their affiliated institutions, Drs Makam, Carlson, and Suh received funding from ICER for the work described in this summary.
Topics: Humans; Amyotrophic Lateral Sclerosis; Cost-Benefit Analysis; Edaravone; Treatment Outcome
PubMed: 36705279
DOI: 10.18553/jmcp.2023.29.2.216 -
Pakistan Journal of Medical Sciences 2023Erythromycin is used for prevention and control of infectious perinatal morbidity. It has been hypothesised that erythromycin crosses the placenta and has an effect on...
OBJECTIVE
Erythromycin is used for prevention and control of infectious perinatal morbidity. It has been hypothesised that erythromycin crosses the placenta and has an effect on the production of placental inflammatory factors. We evaluated the transport of erythromycin in an ex-vivo closed perfusion system of the placenta and determined its effect on the production of placenta inflammatory markers.
METHODS
In 2013, a prospective basic science study was conducted at the placental laboratory of College of Medicine and Health Sciences, United Arab Emirates. Six term placentas from uncomplicated pregnancies were studied using the ex-vivo dual closed-loop human placental cotyledon perfusion technique. Erythromycin was added to the perfusate in the maternal compartment. Samples were obtained from the maternal and fetal up to 240 minutes.
RESULTS
The reference antipyrine was detected in the fetal circulation in the first 15 minutes after addition of the drug. At this point the mean antipyrine was 49.90±2.10μg/ml in the maternal perfusate and 7.1±1.56μg/ml in fetal perfusate. The fetal and maternal concentration became similar at 120 minutes. The transfer of antipyrine from maternal to fetal compartment was 98.66%. The differences between perfusion groups were non-significant that indicates the perfusion of placentas was comparable. After media exchange in both sides, erythromycin was added to the maternal perfusate. The experimental period of four hours was continued with medium circulation on both maternal and fetal circulation. The concentration of erythromycin decreased in the maternal circuit by 36.4% and increased in the fetal circuit by 65%. The concentration of IL-6 in the maternal circuit was normal.
CONCLUSION
Erythromycin crossed the placenta and did not inhibit the production of IL-6. Future studies are needed concerning neonatal adverse effects and the development of antibiotic resistance.
PubMed: 36694753
DOI: 10.12669/pjms.39.1.6683 -
Animal Models and Experimental Medicine Apr 2023We aimed to prepare a non-invasive, reproducible, and controllable rat model of intracerebral hemorrhage with focused ultrasound (FUS).
BACKGROUND
We aimed to prepare a non-invasive, reproducible, and controllable rat model of intracerebral hemorrhage with focused ultrasound (FUS).
METHODS
A rat intracerebral hemorrhage (ICH) model was established by combining FUS and microbubbles (μBs), and edaravone was used to verify whether the free radical scavenger had a protective effect on the model. The brain tissue of each group was sectioned to observe the gross histology, blood-brain barrier (BBB) permeability, cerebral infarction volume, and histopathological changes.
RESULTS
Compared with the FUS group, the BBB permeability was significantly increased in the FUS + μBs (F&B) group (p = 0.0021). The second coronal slice in the F&B group had an obvious hemorrhage lesion, and the FUS + μBs + edaravone (F&B&E) group had smaller hemorrhage areas; however, ICH did not occur in the FUS group. The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group (p = 0.0030) and F&B&E group (p = 0.0208). HE staining results showed that nerve fibrinolysis, neuronal necrosis, microglia production, and erythrocytes were found in both the F&B group and the F&B&E group, but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.
CONCLUSIONS
A rat ICH model was successfully prepared using the μBs assisted FUS treatment, and edaravone had a therapeutic effect on this model. This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.
Topics: Rats; Animals; Rats, Sprague-Dawley; Edaravone; Microbubbles; Cerebral Hemorrhage; Necrosis; Cerebral Infarction
PubMed: 36647712
DOI: 10.1002/ame2.12303 -
Journal of Enzyme Inhibition and... Dec 2023A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (, 1,3,4-thiadiazoles (-, and pyrimidines (-, was preparedand assessed for its potential COX-2...
Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents.
A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (, 1,3,4-thiadiazoles (-, and pyrimidines (-, was preparedand assessed for its potential COX-2 inhibitors. Compared to Celecoxib, compounds and were the most potent derivatives c with a half-maximal inhibitory concentration range of 53-69 nM. Considering COX-2 selectivity index, compounds and were chosen among these most potent derivatives for further investigation. The ability of compounds and to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.
Topics: Humans; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antipyrine; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drug Design; Edema; Molecular Docking Simulation; Structure-Activity Relationship
PubMed: 36633257
DOI: 10.1080/14756366.2022.2162511 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Nov 2022To investigate the effect and mechanism of needle extracts (PNE) on oxidative stress injury in cerebral ischemia reperfusion rats.
OBJECTIVE
To investigate the effect and mechanism of needle extracts (PNE) on oxidative stress injury in cerebral ischemia reperfusion rats.
METHODS
The SD male rats were randomly divided into sham group, model control group, Edaravone (3 mg/kg) group, PNE low-dose (200 mg/kg), medium-dose (400 mg/kg) and high-dose (800 mg/kg) groups. PNE was administered by gavage for 7 d before modeling and 6 h after modeling in PNE treatment groups; Edaravone was given by intraperitoneal injection 7 d before modeling and 6 h after reperfusion. The rat model of cerebral ischemia reperfusion injury was established by middle cerebral artery occlusion method. After 24 h of reperfusion, the neurological deficit score, brain water content and cerebral infarction volume of rats were measured. The pathological changes of cerebral cortex and hippocampus were observed by HE staining, and the number of normal nerve cells was counted. The apoptosis rate of neurons in cerebral cortex was detected by TUNEL method. The content of nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) activity in ischemic brain tissue were detected. The protein expression of c-Jun N-terminal kinase (JNK) 3, phosphorylated JNK3 (p-JNK3), B-cell lymphoma protein(Bcl) -2, Bcl-2 associated X (Bax), cytochrome C and caspase-3 in cerebral cortex were detected by Western blotting method.
RESULTS
Compared with the model control group, the behavioral score, brain water content and cerebral infarction volume in PNE groups were significantly reduced (all <0.05), the pathological damage of cerebral cortex and hippocampal CA1 area was significantly alleviated, and the number of normal nerve cells in ischemic cortex and hippocampal CA1 area was increased (all <0.05). The medium-dose PNE group had the best effect. Compared with the model control group, the apoptosis rate of cortical neurons, the content of NO and MDA in cerebral cortex, the ratio of p-JNK3/JNK3, the expression level of cytochrome C and caspase-3 protein in PNE medium-dose group were significantly reduced , and the activity of SOD, the Bcl-2/Bax ratio were significantly improved (all <0.05).
CONCLUSION
PNE ameliorates brain injury after cerebral ischemia reperfusion in rats, which may be related to scavenging NO and MDA, inhibiting oxidative stress-mediated JNK3/caspase-3 signsal transduction to inhibit neuronal apoptosis.
Topics: Animals; Male; Rats; Apoptosis; bcl-2-Associated X Protein; Brain Ischemia; Caspase 3; Cytochromes c; Edaravone; Infarction, Middle Cerebral Artery; Oxidative Stress; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Signal Transduction; Superoxide Dismutase; Plant Extracts; Pinus
PubMed: 36581582
DOI: 10.3724/zdxbyxb-2022-0326