BACKGROUNDThe functional improvement following bone marrow stromal cells (BMSCs) transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke.

METHODSRat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered saline (PBS) solution to evaluate the expression of stromal cell-derived factor-1 (SDF-1) in ischemic brain, and compared to that in sham group (n = 5/ group/time point[at 1, 3, and 7 days after operation]). The content of chemokine receptor-4 (CXCR4, a main receptor of SDF-1) at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs (2 × 106), or a combination of MCI-186 and BMSCs (n = 10/group). 5-bromo-2-deoxyuridine (BrdU) and Nestin double-immunofluorescence staining was performed to identify the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome.

RESULTSMCI-186 upregulated the expression of SDF-1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI-186, BMSCs, or a combination of MCI-186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group (P < 0.01 or 0.05, respectively). Combination therapy represented a further restoration, increased the number of BMSCs and Nestin+ cells in ischemic brain as compared with BMSCs monotherapy (P < 0.01). The number of engrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain (r = 0.72 , P < 0.01) and the improvement of foot-fault (r = 0.70, P < 0.01).

CONCLUSIONMCI-186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy.

Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Bone Marrow Cells ; cytology ; physiology ; Brain Ischemia ; drug therapy ; metabolism ; therapy ; Chemokine CXCL12 ; metabolism ; Disease Models, Animal ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; therapy ; Male ; Mesenchymal Stromal Cells ; physiology ; Neurogenesis ; physiology ; Rats ; Rats, Sprague-Dawley ; Stroke ; drug therapy ; metabolism ; therapy

No abstract available.
Basophils* ; Dipyrone* ; Hypersensitivity*

BACKGROUNDAntioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs.

METHODSSLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO 3 ) staining at 1, 4, and 6 days.

RESULTSThe ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group.

CONCLUSIONSEdaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

Animals ; Antipyrine ; analogs & derivatives ; chemistry ; Ear, Inner ; drug effects ; injuries ; Female ; Guinea Pigs ; Hearing Loss, Noise-Induced ; prevention & control ; Lipids ; chemistry ; Nanoparticles ; chemistry ; Reactive Oxygen Species ; metabolism

OBJECTIVETo investigate the effect of edaravone on oxidative stress and myocardial fibrosis induced by isoproterenol in rats.

METHODSFifty male SD rats were randomly divided into 5 groups, including a control group, a myocardial fibrosis model (established by injections of isopropyl adrenaline for 10 days) group, and 3 edaravone groups with edaravone treatment at low, medium, or high doses for 14 days. After the treatments, the rats were examined for the degree of myocardial fibrosis, left ventricular mass index (LVMI), collagen volume fraction (CVF), and myocardial contents of collagen I (Col I), collage III (Col III), hydroxyproline (Hyp), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO); The expression of transforming growth factor-β1 (TGF-β1) in the myocardial tissues was examined by immunofluorescence assay and Western blotting.

RESULTSCompared with the control rats, the rat models of myocardial fibrosis showed significantly increased CVF and LVMI (P=0.000), which were lowered by edaravone treatments in a dose-dependent manner (P<0.05). The myocardial contents of Col I, Col III and Hyp also increased in the model group (P=0.000) and were lowered dose-dependently by edaravone; the contents of MDA was higher (P=0.000) and SOD and NO were lower in the model group (P=0.000), and edaravone treatments obviously increased SOD and NO contents (P<0.05). The model rats showed significantly increased myocardial expression of TGF-β1 (P=0.000), which was markedly lowered by edaravone treatments (P=0.000). The myocardial content of MDA was positively correlated while SOD and NO were negatively with LVMI, CVF, Col I, Col III and Hyp; TGF-β1 was positively correlated with LVMI, CVF, Col I, Col III, Hyp and MDA but negatively with SOD and NO.

CONCLUSIONEdaravone can relieve oxidative stress and inhibit TGF-β1 activation to ameliorate myocardial fibrosis in rats.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Cardiomyopathies ; chemically induced ; drug therapy ; Collagen ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; Heart ; drug effects ; Hydroxyproline ; metabolism ; Isoproterenol ; Male ; Malondialdehyde ; metabolism ; Myocardium ; pathology ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVE: To investigate the mechanism of the pulmonary injury in rats caused by chronic intermittent hypoxia (CIH) and to investigate the intervention effect of Edaravone. METHOD: Ninety-six male Wistar rats were divided into four groups randomly: the control group (NC), chronic intermittent hypoxia group (CIH), chronic intermittent hypoxia normal saline matched group (NS), chronic intermittent hypoxia edaravone treatment group (NE). The four groups were also divided into 1, 2, 3, 4 W time subgroups, and each time subgroup had 6 rats. After the experiment, sections of pulmonary were stained with hematoxylin-eosin (HE) and the level of SOD, MDA, PO2 and Ang II mRNA in rat homogenate pulmonary were measured. RESULT: Pulmonary histology revealed that the CIH group showed high levels of interstitial edema, alveolar atelectasis, inflammatory cell infiltration of alveolar epithelial cell, pulmonary injury were serious in 1, 2, 3, 4 W. But the pulmonary histology of the UC group and the NS group was normal. Compared with the NS group, pulmonary injury of NE group 1, 2, 3, 4 W, significantly decreased. Compared with the NC group, the levels of PO2 in the CIH group were decreased; while the compared with the NS group, the levels of PO2 in the NE group were increased. Compared with the UC group and NS group, the levels of Ang II mRNA in each time point in CIH group were increased gradually (P < 0.05), the content of MDA were increased in 1, 2, 3, 4 W (P < 0.05), they had reached the peak all at 4 W; while the SOD in each time point in CIH group were decreased gradually (P < 0.05) compared with that in UC group and NS group; The Ang II mRNA levels of CIH in pulmonary showed positive correlation with MDA [r = 0.782,P < 0.01]; while the Ang II mRNA levels of CIH in pulmonary showed negative correlation with SOD [r = - 0.904, P < 0.01]. CONCLUSION CIH can cause pulmonary injury through oxidative stress and activating Ang II, and Edaravone could prevent pulmonary injury induced by CIH through scavenging oxygen free radicals.
Angiotensin II ; metabolism ; Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Edaravone ; Free Radical Scavengers ; metabolism ; Hypoxia ; physiopathology ; Lung ; pathology ; Lung Injury ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism

OBJECTIVE: To investigate the protective effect of edaravone and danshensu conjugate (IM-009) on focal cerebral ischemia-reperfusion injury in rats and its underlying mechanisms.
 METHODS: Rats were randomly assigned into 6 groups, including a sham group, a model group, an edaravone-treated group, a danshensu-treated group, a low dose of IM-009-treated group and a high dose of IM-009-treated group. The focal cerebral ischemia-reperfusion model was established by intraluminal filament. After the drug treatment, the infarct volume and extent of brain edema were measured. The levels of MDA and SOD were determined by the corresponding assay kit. The scavenging effect of IM-009 on hydroxyl radical and superoxide anion was also measured in a cell free system.
 RESULTS: 1) In comparison with the model group, the infarct volume and water content in rat brain after IM-009 treatment were significantly reduced. The protective effect of IM-009 at higher dose was much stronger than that of edaravone or danshensu (all P<0.05). 2) IM-009 significantly reduced the levels of MDA and increased the activity of SOD (all P<0.05). 3) IM-009 demonstrated strong activities in scavenging .OH and .O(2)(-) (all P<0.05).
 CONCLUSION IM-009 is able to protect rats from ischemia-reperfusion injury. The protective effect of IM-009 could be due to its radical-scavenging action.
Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Brain Edema ; Brain Ischemia ; drug therapy ; Cerebral Infarction ; drug therapy ; Edaravone ; Lactates ; pharmacology ; Malondialdehyde ; metabolism ; Rats ; Reperfusion Injury ; drug therapy ; Superoxide Dismutase ; metabolism

Acute Lung Injury ; drug therapy ; metabolism ; Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Cytokines ; metabolism ; Free Radical Scavengers ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Epidural administration of dexamethasone has been suggested for pain control after minor orthopedic surgery. This study was conducted to assess its efficacy after such surgery, combined or not to IV dipyrone, IV parecoxibe or their combination. METHODS: 91 patients were randomly assigned to seven groups. Patients were submitted to spinal bupivacaine anesthesia combined to epidural administration of either 10 ml saline or 10 mg dexamethasone diluted to 10-ml volume. Patients also received 10 ml IV saline or 1 gr dipyrone and/or 40 mg parecoxibe diluted to 10 ml with saline. Control group (CG) received epidural and IV saline. Dexamethasone group (DexG) received epidural dexamethasone and IV saline. Dipyrone group (DipG) received epidural saline and IV dipyrone. Dex-Dip G received epidural dexamethasone and IV dipyrone. Parecoxibe group (ParG) received epidural saline and IV parecoxibe. Dex-ParG received epidural dexamethasone and IV parecoxibe. Finally, Dex-Dip-ParG received epidural dexamethasone and IV dipyrone plus IV parecoxibe. RESULTS: The CG expressed 4h of analgesia and sooner requested pain killer. DexG was similar to DipG or ParG or Dex-ParG (7-hours), and they requested less ketoprofen compared to the CG (P < 0.05). However, the Dex-DipG and the Dex-Dip-ParG resulted in longer time to demand pain killer (17-hours) and less ketoprofen consumption in 24-hours (P < 0.002). Adverse effects were similar among groups. CONCLUSIONS: The analgesia secondary to epidural dexamethasone was enhanced by IV dipyrone, while no effects were observed by the addition of IV parecoxibe.
Analgesia* ; Anesthesia ; Bupivacaine ; Dexamethasone* ; Dipyrone* ; Humans ; Ketoprofen ; Orthopedics* ; Pain, Postoperative

BACKGROUND: Epidural administration of dexamethasone has been suggested for pain control after minor orthopedic surgery. This study was conducted to assess its efficacy after such surgery, combined or not to IV dipyrone, IV parecoxibe or their combination. METHODS: 91 patients were randomly assigned to seven groups. Patients were submitted to spinal bupivacaine anesthesia combined to epidural administration of either 10 ml saline or 10 mg dexamethasone diluted to 10-ml volume. Patients also received 10 ml IV saline or 1 gr dipyrone and/or 40 mg parecoxibe diluted to 10 ml with saline. Control group (CG) received epidural and IV saline. Dexamethasone group (DexG) received epidural dexamethasone and IV saline. Dipyrone group (DipG) received epidural saline and IV dipyrone. Dex-Dip G received epidural dexamethasone and IV dipyrone. Parecoxibe group (ParG) received epidural saline and IV parecoxibe. Dex-ParG received epidural dexamethasone and IV parecoxibe. Finally, Dex-Dip-ParG received epidural dexamethasone and IV dipyrone plus IV parecoxibe. RESULTS: The CG expressed 4h of analgesia and sooner requested pain killer. DexG was similar to DipG or ParG or Dex-ParG (7-hours), and they requested less ketoprofen compared to the CG (P < 0.05). However, the Dex-DipG and the Dex-Dip-ParG resulted in longer time to demand pain killer (17-hours) and less ketoprofen consumption in 24-hours (P < 0.002). Adverse effects were similar among groups. CONCLUSIONS: The analgesia secondary to epidural dexamethasone was enhanced by IV dipyrone, while no effects were observed by the addition of IV parecoxibe.
Analgesia ; Anesthesia ; Bupivacaine ; Dexamethasone ; Dipyrone ; Humans ; Ketoprofen ; Orthopedics ; Pain, Postoperative

OBJECTIVE: To study DNA quantification and STR typing of samples pre-treated with pyramidon. METHODS: The blood samples of ten unrelated individuals were anticoagulated in EDTA. The blood stains were made on the filter paper. The experimental groups were divided into six groups in accordance with the storage time, 30 min, 1 h, 3 h, 6 h, 12 h and 24h after pre-treated with pyramidon. DNA was extracted by three methods: magnetic bead-based extraction, QIAcube DNA purification method and Chelex-100 method. The quantification of DNA was made by fluorescent quantitative PCR. STR typing was detected by PCR-STR fluorescent technology. RESULTS: In the same DNA extraction method, the sample DNA decreased gradually with times after pre-treatment with pyramidon. In the same storage time, the DNA quantification in different extraction methods had significant differences. Sixteen loci DNA typing were detected in 90.56% of samples. CONCLUSION Pyramidon pre-treatment could cause DNA degradation, but effective STR typing can be achieved within 24 h. The magnetic bead-based extraction is the best method for STR profiling and DNA extraction.
Aminopyrine/pharmacology* ; Blood Stains ; DNA/isolation & purification* ; DNA Fingerprinting ; Forensic Medicine ; Humans ; Polymerase Chain Reaction ; Reproducibility of Results ; Specimen Handling