[Flavonoids of puerarin versus tanshinone II A for ischemic stroke: a randomized controlled trial].

BACKGROUND: Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest. OBJECTIVE: To investigate the therapeutic effects and functions of flavonoids of puerarin in treating patients with ischemic stroke. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 67 inpatients suffering from ischemic stroke from the Department of Neurology, Changhai Hospital in China were divided into two groups randomly, the treatment group, which was treated with flavonoids of puerarin, and the control group, administered with tanshinone II A sulfate instead. MAIN OUTCOME MEASURES: Defects in neurological function were evaluated according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of onset. Lactate dehydrogenase (LDH), serum interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) levels were determined by radioimmunoassay on the second trial day. After a 14-day treatment, LDH, serum IL-6 and BDNF levels and NIHSS score were also detected, and CT perfusion imaging was used to measure and analyze the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). RESULTS: On the first day, NIHSS scores of the two groups were similar. On the second day there was no significant difference in LDH and IL-6 levels between the treatment group and the control group. After a 14-day treatment, LDH and IL-6 levels and the NIHSS score in the treatment group were lower than those in the control group (P<0.05). There was no significant difference in BDNF levels in the two groups. After 14 d, the CT perfusion imaging demonstrated that the treatment group showed more effective blood perfusion than the control group. CONCLUSION: Flavonoids of puerarin can restrain the increase of IL-6 after acute ischemic stroke, and depress the LDH raised by reperfusion after cerebral ischemia. It can also enhance blood perfusion of the ischemic region.

[Anti-oxidant effects of Tongxinluo on ATPase in focal brain ischemia-reperfusion rats].

OBJECTIVE: To explore the effects of Tongxinluo on adenosine triphosphatase (ATPase), anti-oxidant enzymes activities, and lipid peroxidation of mitochondria or brain homogenate in focal brain ischemia-reperfusion rats. METHODS: The models of the focal brain ischemia-reperfusion rats were made by the middle cerebral artery occlusion (MCAO). Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and ATPase and malonaldehyde (MDA) levels of mitochondria or brain homogenate were measured by biochemical methods. RESULTS: Tongxinluo significantly inhibited the decrease of activities of SOD and the increase of MDA levels, but had no difference in GSH-Px in brain homogenate. It also inhibited the decrease of activities of SOD, GSH-Px, ATPase, and the increase of MDA levels in mitochondria. CONCLUSION: The protective mechanisms of Tongxinluo against mitochondrial injuries in focal ischemia-reperfusion rats may be derived from reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.

[The alpha-synuclein gene microsatellite polymorphism and late-onset sporadic Parkinson's disease susceptibility].

OBJECTIVE: To explore the association of the microsatellite polymorphisms in the promoter region of alpha-synuclein gene with the late-onset sporadic Parkinson's disease (PD) susceptibility. METHODS: The microsatellite polymorphism of alpha-synuclein gene was analyzed with amplified fragment length polymorphism (Amp-FLP) and semiautomatic fluorescent labeled genotyping technique. Association analysis was performed in 135 unrelated late-onset sporadic PD patients and 170 age-matched healthy controls. RESULTS: The distribution of the alleles of the dinucleotide repeats variants of alpha-synuclein gene promoter region in PD cases was significantly different from that in the healthy controls. The most frequent allele in PD patients was allele 269 bp, but in controls it was the 271 bp allele. Alleles of

[A pedigree with myotonic dystrophy: non-CTG, non-CCTG repeat expansion].

OBJECTIVE: Two genetic loci are associated with the myotonic dystrophy (DM) phenotype: DM1 DMPK on chromosome 19, and DM2 ZNF9 on chromosome 3. The aim of this study was to investigate the molecular genetics of a pedigree with DM. METHODS: In twenty-six individuals from a family with DM, the CTG repeats in DMPK and CCTG repeats in ZNF9were evaluated genetically, using Long Expand trade mark Template polymerase chain reaction (PCR), Southern blotting and genomic scanning. RESULTS: The numbers of CTG and CCTG repeat were all in normal range. There was no significant difference between the CTG repeat size in DMPK gene and that 4 years later from the same individual. The Lod score values with short tandem repeats STR markers chosen in 19q and 3q were all smaller than 1, which suggested that no STR marker was linked with this DM family. CONCLUSION: There might be some other mutant in this DM pedigree. Further study should be done to find the genetic basis of this pedigree.

[Endovascular stent-assisted angioplasty for atherosclerotic intracranial stenosis, a clinical analysis of 39 cases].

OBJECTIVE: To assess the preliminary outcome of endovascular stent-assisted angioplasty for intracranial stenosis. METHODS: Thirty-nine patients with atherosclerotic intracranial stenosis (19 cases in posterior circulation and 20 in anterior circulation) were treated with endovascular angioplasty using balloon-expandable coronary stents. Follow-up was made for 4 - 24 months. The clinical manifestations were observed and CT, MR, or DSA were conducted before and after the operation. RESULTS: All of the stents were successfully implanted on the first procedure without procedural and periprocedural complications. The mean carotid artery stenosis rate was 73.5 +/- 6.7% before the procedure and 11.2 +/- 4.3% after the procedure. The patients were clinical asymptomatic and neurologically intact. Follow-up angiographies made in 29 patients revealed no restenosis. CONCLUSION: With effective short-term results and helpful in decreasing incidence of stroke, endovascular stenting is safe and feasible for treatment of intracranial stenosis.

Effects of L-lysine monohydrochloride on insulin and blood glucose levels in spinal cord injured rats.

BACKGROUND: Hyperglycemia in brain and spinal cord could aggravate neurologic impairment. Recent studies showed that L-lysine monohydrochloride (LMH) could increase the insulin secretion and regulate the blood glucose level. The aim of the present study was to investigate the effects of LMH on pancreatic islet B cells, the levels of endogenous insulin and blood glucose in spinal cord injured rats. METHODS: Forty male Wistar rats were divided into four groups, namely, normal control group, model group, high-dose LMH group (621.5 mg/kg equal to LMH 1/8 LD50), and low-dose LMH group (310.8 mg/kg equal to LMH 1/16 LD50). The model of spinal cord injured rat was established by hemi-transection at the lower right thoracic spinal cord. LMH was administered via intraperitoneal injection once spinal cord injury was produced in rats. All rats were sacrificed 48 hours after spinal cord injured. The effects of LMH on pancreatic islet B cells, the content of endogenous insulin, and the level of blood glucose were observed with immunohistochemical method, radioimmunoassay method, and biochemical analyzer, respectively. RESULTS: The insulin immunohistochemical intensities of islet B cells were significantly weaker in model group than those in normal control group (P < 0.01). The levels of endogenous insulin were significantly lower and the blood glucose levels were significantly higher in model group than those in normal control group (P < 0.01). The insulin immunohistochemical intensities of islet B cells were significantly stronger in high-dose LMH group than those in model group (P < 0.05). In addition, we found that the levels of endogenous insulin were significantly higher and the blood glucose levels were significantly lower in high-dose LMH group than those in model group (P < 0.05). There were no significant differences in the insulin immunohistochemical intensities of islet B cells, the levels of endogenous insulin and the blood glucose between low-dose LMH group and model group (P > 0.05). CONCLUSION: LMH, but dose-dependent, might participate in the regulation of pancreatic islet B cells, and then reduce the blood glucose levels in the spinal cord injured rats.

Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats.

OBJECTIVE: To investigate the correlation of perihematomal free radical level and neuronal apoptosis following the intracerebral hemorrhage (ICH). METHODS: Animals were randomly divided into 4 groups: sham operation group, model group, 1 mg/kg edaravone group, and 3 mg/kg edaravone group. Each group was then divided into seven subgroups, in which the rats were correspondingly killed at 6 h, 12 h, 24 h, 48 h, 72 h, 7 d or 14 d (n = 1 in each subgroup of the sham group, and n = 6 in each subgroup of the other 3 groups). By Horseley-Clarke technique, autoblood (80 microL) were administered into the left caudate putamen of SD rats in a double administration-withdrawal way. Rats in the sham group were needled in but not administered with autoblood. The ICH model was then evaluated by Bederson's scale. Around the hematoma, the levels of malonaldehyde (MDA) and hydroxyl radical were tested by spectrophotometer, and the process of apoptosis was tested by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method. RESULTS: (1) ICH significantly increased the levels of MDA and hydroxyl radicals. Significant differences in MDA and hydroxyl radical contents were observed among the four groups. (2) In the sham group, a small number of TUNEL-positive cells were found. In the other three groups, the TUNEL-positive cells were observed at 6 h, increased significantly at 24 h, and reached peak level at 3 d, then fell profoundly at 7 d, but remained detectable at 14 d. (3) The positive correlation existed between apoptosis and free radical level (r = 0.2003), and existed between apoptosis and MDA content (r = 0.6563) in the brain. CONCLUSION: Post-hemorrhagic apoptosis was related to the production of free radicals, indicating that the elevated free radicals following the ICH could induce neuron and glial cell apoptosis.

Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1 alpha and erythropoietin.

OBJECTIVE: To investigate whether desferoxamine (DFO) preconditioning can induce tolerance against cerebral ischemia and its effect on the expression of hypoxia inducible factor 1alpha (HIF-1alpha) and erythropoietin (EPO) in vivo and in vitro. METHODS: Rat model of cerebral ischemia was established by middle cerebral artery occlusion with or without DFO administration. Infarct size was examined by TTC staining, and the neurological severity score was evaluated according to published method. Cortical neurons were cultured under ischemia stress which was mimicked by oxygen-glucose deprivation (OGD), and the neuron damage was assessed by MTT assay. Immunofluorescent staining was employed to detect the expressions of HIF-1alpha and EPO. RESULTS: The protective effect induced by DFO (decreasing the infarction volume and ameliorating the neurological function) appeared at 2 d after administration of DFO (post-DFO), lasted until 7 d and disappeared at 14 d (P < 0.05); the most effective action was observed at 3 d post-DFO. DFO induced tolerance of cultured neurons against OGD: neuronal viability was increased 23%, 34%, 40%, 48% and 56% at 8 h, 12 h, 24 h, 36 h, and 48 h, respectively, post-DFO (P < 0.05). Immunofluorescent staining found that HIF-1alpha and EPO were upregulated in the neurons of rat brain at 3 d and 7 d post-DFO; increase of HIF-1alpha and EPO appeared in cultured cortex neurons at 36 h and 48 h post-DFO. CONCLUSION: DFO induced tolerance against focal cerebral ischemia in rats, and exerted protective effect on OGD cultured cortical neurons. DFO significant induced the expression of HIF-1alpha and EPO both in vivo and in vitro. DFO preconditioning can protect against cerebral ischemia, which may be associated with the synthesis of HIF-1alpha and EPO.