The term "fixed drug eruption" was coined by Louis Brocq in 1894 to describe a special type of reaction to antipyrine. It is now known that many drugs can cause a fixed drug eruption. Notorious offenders have included phenolphthalein, quinine and barbiturates. We present a case of multiple fixed drug eruption appearing in a 20 year-old male patient who has generalized slate-blue colored pigmentation on neck, trunk and extremities. The area of total pigmented skin lesions are over 50% of body surface. We could confirm the fixed drug eruption by positive phenobarbital provocation test.
Antipyrine ; Barbiturates ; Criminals ; Drug Eruptions* ; Extremities ; Humans ; Male ; Neck ; Numismatics ; Phenobarbital ; Phenolphthalein ; Pigmentation ; Quinine ; Skin ; Young Adult

A fixed drug eruption is a cutaneous reaction caused by various drugs, which include phenazone derivatives, barbiturates, sulfonamides, tetracyclines and phenolphthaleins. An eruption caused by piroxicam is very rare and there have been no previous reports in Korea. A 49-year-old woman was seen with mutiple erythematous patches and some bullae that appeared after oral administration of piroxicam. The patient had had two similar episodes after oral administration of piroxicam. We performed patch test with piroxicam and could confirm a fixed drug eruption caused by this durg.
Administration, Oral ; Antipyrine ; Barbiturates ; Drug Eruptions* ; Female ; Humans ; Korea ; Middle Aged ; Patch Tests ; Phenolphthalein ; Phenolphthaleins ; Piroxicam* ; Sulfonamides ; Tetracyclines

OBJECTIVETo explore the electrophysiological properties of differentiation of rat bone marrow-derived stromal stem cells (rBMSCs) to neuron-like cells in vitro by edaravone, a new type of free radical scavenger.

METHODSStromal stem cells were separated from rat bone marrow with Ficoll-Paque reagent and expanded in different culture medium in vitro. rBMSCs were induced by edaravone containing serum-free L-DMEM. Morphologic observation and Western blot analysis including the expression of Nav1.6, Kv1.2, Kv1.3, Cav1.2 were performed, and whole patch-clamp technique was used.

RESULTSCyton contraction and long processes were shown in differentiated stromal stem cells. Nav1.6, Kv1.2, Kv1.3 and Cav1.2 were expressed in both differentiated and undifferentiated cells. However, the expression of channel proteins in differentiated cells was up-regulated. Consistently, their resting potential and outward currents were also enhanced in the differentiated cells, which was especially significant in the outward rectifier potassium current.

CONCLUSIONIn vitro, neuron-like cells derived from rBMSCs, induced by edaravone, possess electrophysiological properties of neurons.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Blotting, Western ; Bone Marrow Cells ; cytology ; physiology ; Cell Differentiation ; drug effects ; Male ; Neurons ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Stromal Cells ; cytology ; physiology

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

OBJECTIVETo explore the effect of extracellular signal regulated kinase 1/2 (ERK1/2) on edaravone (EDA)-triggered protection against myocardial toxicity induced by isoprenaline (ISO) in H9c2 myocardial cells (H9c2 cells).

METHODSH9c2 cells were exposed to ISO at different concentrations to establish a cardiac toxicity model induced by persistent excitation of β1 receptor. EDA was added before ISO as a pretreatment. PD-98059, an ERK1/2 inhibitor, was administered 1 h prior to EDA to inhibit the phosphorylation of ERK1/2. Cell viability was measured using cell counter kit (CCK-8). The expressions of p-ERK1/2 and t-ERK1/2 were tested by Western blotting. Mitochondrial membrane potential (MMP) was detected by Rhodamine123 (Rh123) staining and photofluorography.

RESULTSExposure of H9c2 cells to 80 µmol/L ISO for 24 h down-regulated ERK1/2 phosphorylation and repressed MMP. Pretreatment with 10-40 µmol/L EDA for 1 h inhibited ISO-induced myocardial toxicity and pretreatment of 40 µmol/L EDA partially rescued ERK1/2 phosphorylation and MMP level. PD-98059 abolished cardiac protection of EDA, leading to myocardial toxicity and MMP loss.

CONCLUSIONEDA can protect H9c2 cells against myocardial injury induced by ISO by suppressing ISO-triggered inhibition of ERK1/2 activation.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Cell Line ; Flavonoids ; pharmacology ; Isoproterenol ; toxicity ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Phosphorylation ; Rats

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 observe the expression of GRP78 (glucose regulated protein, GRP78), Caspase-12 and the change of neuron apoptosis in the juvenile rat hippocampus after status convulsive (SC), and to explore the effect of edaravone on them.

METHODSOne hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into normal saline control group (NS group), status convulsive group (SC group) and edaravone treatment group (ED group). Each group was further divided into five subgroups in different executed time points after SC. The rats in status convulsive group were kindled into epilepsy by lithium-pilocarpine method. Expression of GRP78 mRNA and caspase-12 mRNA was detected with reverse transcription-polymerase chain reaction (RT-PCR) method. Expressions of GRP78 and caspase-12 protein were detected with immunohistochemical methods. The neuron apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL).

RESULTS(1) Measured by immunohistochemistry the value of OD of GRP78 (0.1480 ± 0.0164, 0.1682 ± 0.0114, and 0.1540 ± 0.0102, respectively, 12 h - 48 h points) and caspase-12 (0.1325 ± 0.0165, 0.1794 ± 0.0213, 0.1525 ± 0.0423, and 0.1309 ± 0.0199, respectively, 12 h-72 h points) positive cells in the SC group increased, there was a significant difference compared with NS group (GRP78: 0.1214 ± 0.0147, 0.1272 ± 0.0177, and 0.1260 ± 0.0157, respectively, 12 h-72 h points. Caspase-12: 0.1050 ± 0.0121, 0.1041 ± 0.0151, 0.1058 ± 0.0222, and 0.1036 ± 0.0186, respectively, 12 h - 72 h points) (P < 0.01, or P < 0.05). By ED intervention GRP78 (0.1550 ± 0.0131, 0.1886 ± 0.0154, and 0.1721 ± 0.0151, respectively, 12 h - 48 h points) positive cells value of the OD increased as compared with SC group (P < 0.01, or P < 0.05). and caspase-12 (0.1211 ± 0.0184, 0.1545 ± 0.0205, and 0.1085 ± 0.0219, respectively, 12 h, 24 h and 72 h points) positive cells value of the A decreased as compared with SC group (P < 0.01, or P < 0.05). (2) Measured by RT-PCR, the expression of GRP78 mRNA and caspase-12 mRNA trend was similar to protein. (3) The TUNEL positive cells in hippocampus CA(1) of SC group (11.41 ± 2.37) were more than that of NS group after the SC 12 h (P < 0.01), reached its highest level at 48 h (28.78 ± 5.11), after the intervention with edaravone (8.98 ± 2.22, 13.09 ± 2.54 and 20.57 ± 4.89, respectively, 12 h-48 h points), TUNEL positive cells showed a significant drop in SC group at 12 h-48 h time points (P < 0.01, or P < 0.05), but still significantly higher than that of the NS group (6.22 ± 1.50, 6.57 ± 1.61 and 6.72 ± 1.14, respectively) (P < 0.01, or P < 0.05), at the 4 h time point (NS group 6.29 ± 1.49, SC group 6.61 ± 1.71, ED group 5.75 ± 1.41) among the three groups, no significant difference in TUNEL positive cells was found (P = 0.759).

CONCLUSIONSThe expression of GRP78 and caspase-12 increased after SC. Edaravone increased expression of GRP78 and decreased expression of caspase-12 in hippocampus rat with pilocarpine-induced seizures, reduced the number of neuronal apoptosis. These results suggest that edaravone may have protective effect against the hippocampal damage caused by status convulsive.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Apoptosis ; drug effects ; Caspase 12 ; metabolism ; Heat-Shock Proteins ; metabolism ; Hippocampus ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Seizures ; metabolism

OBJECTIVETo investigate the effect of edaravone on renal ischemia-reperfusion injury in rats.

METHODSFifty rats were randomly divided into five groups: sham operation group (Group A), renal ischemia-reperfusion group (Group B) and edaravone treated groups (Group C1, Group C2 and Group C3 with different drug dosages). Serum maleic dialdehyde (MDA) and superoxide dismutase (SOD), renal MDA and SOD, serum creatinine (Cr), blood urea nitrogen (BUN) were measured after the rat kidney was ischemia-reperfused for 24 hours. Renal ultrastructure was observed.

RESULTCompared with Group A, serum and renal MDA, serum Cr, BUN of Group B were significant increased (P <0.01), serum and renal SOD of Group B were significant decreased (P <0.01). After edaravone treatment, serum MDA, Cr and renal MDA of Group C were lower than those in Group B (P<0.01); Serum and renal SOD of group C were higher than those in Group B (P <0.01); Compared with Group B, BUN level of Group C had no significant change (P >0.05). The renal ultrastructure was greatly injured in Group B, meanwhile it was obviously ameliorated in Group C.

CONCLUSIONEdaravone has protective effects on renal ischemia-reperfusion injury in rats.

Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Kidney ; blood supply ; Male ; Malondialdehyde ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; prevention & control ; 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

BACKGROUNDThe underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.

METHODSOne hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.

RESULTSThe rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05).

CONCLUSIONSThis study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.

Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Blotting, Western ; Brain Injuries ; drug therapy ; etiology ; Immunohistochemistry ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; physiopathology ; Superoxide Dismutase ; metabolism